Objective: This study is to observe the effects of Salvia miltiorrhiza injection on blood pressure and cardiac function in rats with pregnancy-induced hypertension and preeclampsia. Methodology: Syncytiotrophoblast mi...Objective: This study is to observe the effects of Salvia miltiorrhiza injection on blood pressure and cardiac function in rats with pregnancy-induced hypertension and preeclampsia. Methodology: Syncytiotrophoblast microvilli (stbm) and l-arginine nitrosyl methyl ester were screened out via caudal vein injection. Twenty gestational hypertension-preeclampsia model SD (Sprague Dawley) rats successfully induced by L-NAME (L-arginine Nitrosyl methyl ester) were randomly divided into 2 groups (model group and Danshen injection group, n = 10). Then another 10 normal pregnant SD rats without model were selected as blank control group. The Salvia miltiorrhiza injection group was given Salvia miltiorrhiza injection (0.5 g?kg?1?d?1) through tail vein, and the control group and model group were given equal volume of normal saline through tail vein injection. All three groups were treated by tail vein injection once a day (d) for 7 days. After treatment, heart rate (HR), Systolic pressure (SP), diastolic pressure (DP) and mean arterial pressure (MAP) were measured by tail artery. Left ventricular end-diastolic diameter (LVDd) and Left ventricular end systolic diameter (LVDs) were recorded by echocardiography. Left ventricular end diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), left ventricular ejection fraction (left ventricular ejection) fraction, LVEF) and the maximum rate of increase/decrease of left ventricular pressure during isovolemic systole (+dp/dtmax/?dp/dtmax);Endothelin-1 (ET-1) levels in rat tail vein blood were detected by ELISA. Results: SP, DP, MP, HR, LVSP, LVDs and ?dp/dtmaxx were all decreased, plasma ET-1 expression was low, and LVDd, LVEDP, LVEF, and +dp/dtmax were all increased in the Salvia miltiorroot injection group, with statistical significance compared to the model group (p Conclusion: Salvia miltiorrhiza injection can improve the cardiac function and reduce blood pressure in rats with pregnancy-induced hypertension and preeclampsia, and the mechanism may be related to alleviating systemic arteriolar spasm by regulating ET-1 level.展开更多
Hypertension and metabolic syndrome, both of which increase with age, are multifactorial disorders. Their etiology is complex, making it challenging to isolate involved genes. This study aimed to characterize the hepa...Hypertension and metabolic syndrome, both of which increase with age, are multifactorial disorders. Their etiology is complex, making it challenging to isolate involved genes. This study aimed to characterize the hepatic gene expression in spontaneously hypertensive rats (SHR) at different ages. Blood pressure in SHR was determined by tail-cuff method at one and three months of age. Hepatic RNA was isolated and gene expression was compared using microarrays. Comparison between SHR and normotensive rats revealed significant variation in gene expression: 98 genes were upregulated and 122 were downregulated in SHR;while 88 genes were upregulated and 139 genes were downregulated in age-matched normotensive rats. Furthermore, within the SHR group, 110 genes were found to be upregulated and 168 genes downregulated across different ages. Analyses via the Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways revealed that several genes are potentially implicated in both, hypertension and metabolic syndrome. The results suggest that SHR display variations in gene expression due to aging, and when compared to normotensive rats. These variations could contribute to the development of hypertension and metabolic syndrome. Microarray studies involving older rats are necessary to further validate these findings.展开更多
Objective:To study the influence of bone marrow mesenchymal stem cells(MSCs)transplantation on hypoxic pulmonary hypertension(HPH)in rats.Methods:MSCs in SD rats were separated,cultivated,identified in vitro,and label...Objective:To study the influence of bone marrow mesenchymal stem cells(MSCs)transplantation on hypoxic pulmonary hypertension(HPH)in rats.Methods:MSCs in SD rats were separated,cultivated,identified in vitro,and labeled by the green fluorescence protein(GFP)adenovirus.Healthy male SD rats were randomly divided into four groups:normal control group(NC group)and HPH group,with eight rats in each group respectively;HPH+mesenchymal stem cell transplantation group(MSCs group)and HPH+vascular endothelial growth factor+mesenchymal stem cell transplantation group(VEGF+MSCs group),with twenty-four rats in each group respectively.In this experiment,intermittent normobaric hypoxia was employed to establish the pulmonary hypertension rat models,with stem cells transfected and transplanted.The mean pulmonary artery pressure(mPAP)was observed in rats to calculate the right ventricular hypertrophy index(RVHI);the morphological changes of pulmonary arterioles in each group of rats were observed under the microscope;the distribution and manifestation of MSCs fluorescently labeled by adenovirus transfection were observed in pulmonary arterioles under the fluorescence microscope at the set time points of 7 d,14 d and 28 d after the transplantation of stem cells.Results:For NC group,the mPAP(mmHg)was 15.5±1.5 at 28 d,while the mPAP in HPH,MSCs and VEGF+MSCs groups were 26.1±1.9,21.6±2.7 and 20.1±2.9 respectively which were apparently higher than that in NC group(p<.01).Compared with HPH group(p<.01),the mPAP was obviously decreased in MSCs and VEGF+MSCs groups.There was no significant difference between MSCs and VEGF+MSCs groups.At 28 d,RVHI for NC group was 0.28±0.02,while the RVHI in HPH,MSCs and VEGF+MSCs groups were 0.43±0.07,0.34±0.03 and 0.35±0.01 respectively which were apparently higher than that in NC group(p<.01).In comparison with HPH group,RVHI was significantly decreased in MSCs and VEGF+MSCs groups(p<.05).There was no significant difference between MSCs and VEGF+MSCs groups.For HPH group,at 28 d,pulmonary arterioles were apparently thickened,with luminal stenosis&obliteration and incomplete endothelial cells.Compared with HPH group,pulmonary arterioles in MSCs group became thinning,with the lumen unobstructed and the integrity of endothelial cells improved.The changes in the manifestation of MSCs and VEGF+MSCs groups were not significant.Conclusions:The transplantation of MSCs can improve the remodeling of pulmonary arterioles to partially reverse the progress of HPH;the combined transplantation of VEGF and MSCs doesn’t improve the effect of MSC transplantation.展开更多
BACKGROUND : The importance of nitric oxide (NO) in the pathogenesis of portal hypertension (PHT) has been extensively studied, but whether or not prostacyclin (PGI2) plays a role in formation and development of hyper...BACKGROUND : The importance of nitric oxide (NO) in the pathogenesis of portal hypertension (PHT) has been extensively studied, but whether or not prostacyclin (PGI2) plays a role in formation and development of hyperdynamic circutatory state in PHT has not been verified. The present study was undertaken to investigate the possible interaction between prostacyclin (PGI2) and nitric oxide (NO) in the hyperdynamic circulatory state of rats with chronic portal hypertension (PHT), by measuring the hemodynamic changes and expression of cyclooxygenase (COX) mRNA in vessels and small intestine after administration of Nω- nitro-L-arginine (L-NNA) or indomethacin (INDO) either in the short-term (7 days) or long-term (15 days). METHODS: Ninety-seven male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) induced by injection of CCl4, prehepatic portal hypertension (PHPH) induced by partial stenosis of the portal vein, and sham-operated controls (SO). Animals of each group received L-NNA or INDO either for 7 or 15 days, with saline as control. Splanchnic hemodynamics was measured by the radioactive microsphere technique. The concentration of NO in serum was determined as the nitrate; nitrite ratio (NO2-/NO3-, μmol/L) by a colorometric method, and that of PGI2 was measured by specific radioimmunoassay for its stable hydrolysis product 6-keto-PGF1α (pg/ml). The reverse transcription- polymerase chain reaction measured the levels of COX-1 mRNA in the superior mesenteric artery, thoracic aorta, and small intestine of these rats.RESULTS: Compared with SO rats, COX-1 mRNA expression and the concentrations of plasma 6-keto- PGF1α and serum NO2-/NO3- were enhanced in both IHPH and PHPH rats; splanchnic vascular resistance (SVR) decreased, but portal venous inflow (PVI) markedly increased (P<0.05). Seven or 15 days of L-NNA treatment reduced COX-1 mRNA expression in these vessels and the small intestine, concomitant with a significant decrease in the concentration of plasma PGI2 and serum NO in IHPH and PHPH rats (P<0.05). At the same time, PVI decreased but SVR increased significantly (P<0.05). In both IHPH and PHPH rats, the COX-1 mRNA expression and the concentration of plasma PGI2 after No synthase (NOS) blockade for 15 days were higher than those for 7 days, whereas the hyperdynamic circulatory state was improved after NOS blockade for 15 days compared with 7 days. The concentration of PGI2 treated by INDO for 15 days was not significantly different from that after 7-day COX blockade, and hemodynamics restored hyperdynamic circulatory state. CONCLUSIONS: The hyperdynamic circulatory state in rats with PHT is correlated with the concentration of serum NO. There is a possible interaction between PGI2 and NO in the hyperhemodynamics of PHT. PGI2 is probably not the mediator in the formation and development of the hyperdynamic circulatory state in rats with chronic PHT.展开更多
Intravenous and intratracheal implantation of mesenchymal stem cells (MSCs) may offer ameliorating effects on pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. The aim of this study was to examine th...Intravenous and intratracheal implantation of mesenchymal stem cells (MSCs) may offer ameliorating effects on pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. The aim of this study was to examine the anti-remodeling effect of intravenous MSCs (VMSCs) and intratracheal MSCs (TMSCs) in rats with PH, and the underlying mechanisms. MSCs were isolated from rat bone marrow and cultured. PH was induced in rats by intraperitoneal injection of MCT. One week after MCT administration, the rats were divided into 3 groups in terms of different treatments: VMSCs group (intravenous injection of MSCs), TMSCs group (intratracheal injection of MSCs), PH group (no treatment given). Those receiving saline instead of MCT served as negative control (control group). Pulmonary arterial structure was pathologically observed, pulmonary arterial dynamics measured, and remodeling-associated cytokines Smad2 and Smad3 detected in the lungs, three weeks after MCT injection. The results showed that PH group versus control group had higher pulmonary arterial pressure (PAP) and wall thickness index (WTI) 21 days after MCT treatment. The expression of phosphorylated (p)-Smad2 and the ratio of p-Smad2/Smad2 were much higher in PH group than in control group. Fluorescence-labeled MSCs were extensively distributed in rats’ lungs in VMSCs and TMSCs groups 3 and 14 days after transplantation, but not found in the media of the pulmonary artery. WTI and PAP were significantly lower in both VMSCs and TMSCs groups than in PH group three weeks after MCT injection. The p-Smad2 expression and the ratio of p-Smad2/Smad2 were obviously reduced in VMSCs and TMSCs groups as compared with those in PH group. In conclusion, both intravenous and intratracheal transplantation of MSCs can attenuate PAP and pulmonary artery remodeling in MCT-induced PH rats, which may be associated with the early suppression of Smad2 phosphorylation via paracrine pathways.展开更多
AIM: To evaluate effect of hypertension on retinal ganglion cell(RGC) apoptosis, intraocular pressure(IOP),and the activation of endothelin-1(ET-1) signaling pathway in central retinal artery(CRA) in rats.MET...AIM: To evaluate effect of hypertension on retinal ganglion cell(RGC) apoptosis, intraocular pressure(IOP),and the activation of endothelin-1(ET-1) signaling pathway in central retinal artery(CRA) in rats.METHODS: The experimental study was performed on20 male Sprague Dawley rats that were divided into control group, and hypertension groups. The hypertension was induced by subcutaneous deoxycorticoacetate(DOCA)10 mg/kg twice a week and administered 0.9% Na Cl solution daily for 2, 6, and 10 wk. Blood pressure(BP) was measured using animal BP analyzer. IOP was measured by handheld tonometry. Retinal tissue preparations by paraffin blocks were made after enucleation. The expression of ET-1, e NOS, ET-1 receptor A(ETRA), ET-1receptor B(ETRB), and phosphorylated myosin light chain kinase(MLCK), and caldesmon(Ca D) in CRA and RGC apoptosis were evaluated through immunofluorescent staining method then observed using laser scanning confocal microscopy. RESULTS: BP significantly increased in all of the hypertension groups compared to control(P =0.001).Peak IOP elevation(7.78±4.14 mm Hg) and RGC apoptosis(576.15±33.28 Au) occurred on 2wk of hypertension. ET-1expression(1238.6±55.1 Au) and e NOS expression(2814.2±70.7 Au) were found highest in 2wk of hypertension,although the ratio of ET-1/e NOS decreased since 2wk.ETRAreached peak expression in 10 wk of hypertension(1219.4 ±6.3 Au), while ETRBsignificantly increased only in 2 weeks group(1069.2 ±9.6 Au). The highest MLCK expression(1190.09±58.32 Au), Ca D(1670.28±18.36 Au)were also found in 2wk of hypertension.CONCLUSION: Hypertension effects to activation of ET-1 signaling pathway significantly in CRA, elevation of IOP, and RGC apoptosis. The highest value was achieved at 2wk, which is the development phase of hypertension.展开更多
Pulmonary arterial hypertension (PAH) is a progressive disease associated with increased constriction and remodeling of the pulmonary vasculature. Quercetin is a natural fiavonoid and has a variety of pharmacologica...Pulmonary arterial hypertension (PAH) is a progressive disease associated with increased constriction and remodeling of the pulmonary vasculature. Quercetin is a natural fiavonoid and has a variety of pharmacological effects including improvement of endothelial cell function. However, its pharmacological effects on pulmonary hypertension have been rarely reported. We sought to observe the protective effect of quercetin in rats with monocrotaline induced PAH. We divided 30 male Sprague-Dawley rats randomly into three groups with ten rats in each group: the monocrotaline group, the quercetin group and the control group. We found that, compared with the controls, the mean pulmonary artery pressure (mPAP) and the right ventricular hypertrophy index in the monocrotaline group were significantly higher (P 〈 0.01). Quercetin caused a significant reduction both in the mPAP and fight ventricular hypertrophy index compared with the monocrotaline group (P 〈 0.01) while no difference was found between the quercefin group and the control group (P 〉 0.05). Monocrotaline induced a marked increase in the wall thickness (WT) in small and mid-sized pulmonary arteries compared with the controls (P 〈 0.01). Monocrotaline also induced a marked increase in the wall area (WA) in small [(56.38 ±6.65)% in monocrotaline vs. (19.80±4.63)% in control] and mid-sized [(43.71± 5.38)% in monocrotaline vs. (14.24± 3.66)% in control] pulmonary arteries (P 〈 0.01). Quercefin treatment markedly reduced monocrotaline induced increase in both WT and WA (P 〈 0.01), which, however, still remained significantly elevated compared with those of the controls (P 〈 0.01). Furthermore, compared with controls, proliferating cell nuclear antigen (PCNA) expression in the pulmonary artery tissues was markedly increased by monocrotaline [(45.59± 1.27) in monocrotaline vs. (9.64± 0.69) in controls], which was significantly attenuated by quercetin. Our animal experiment indicated that quercetin could have protective effects on monocrotaline-induced PAH.展开更多
Objective: Long-term intake of Miso attenuates hypertension in Dahl salt-sensitive (Dahl S) rats through an increased urinary sodium excretion. We examined whether a bolus injection into the peritoneal cavity (i.p.) o...Objective: Long-term intake of Miso attenuates hypertension in Dahl salt-sensitive (Dahl S) rats through an increased urinary sodium excretion. We examined whether a bolus injection into the peritoneal cavity (i.p.) or a continuous subcutaneous infusion of a Miso extract attenuates hypertension in Dahl S rats. Materials and Methods: We investigated the effects of a bolus, i.p. injection of 50 mg Miso extract in 0.5 mL on hypertension in Dahl S rats, and examined whether a long-term subcutaneous infusion of the Miso extract (50 mg Miso/day), using an osmotic mini-pump working for 14 days, attenuates hypertension in Dahl S rats. Results: A bolus, i.p. injection of 50 mg Miso extract decreased SBP in 2 hrs. The reduction was significant at 4 hrs, and SBP returned to the baseline at 24 hrs. The SBP reduction at 4 hrs after the injection was increasingly greater each day during the 4 days. The SBP reduction by the Miso extract was dose-dependent and the antihy-pertensive activity occurs in a <5 kDa fraction of the extract. The subcutaneous infusion of 50 mg Miso extract/day for 14 days significantly attenuated hypertension in Dahl S rats. The SBP reduction was associated with significant decreases in the heart and kidney weights. Urinary protein excretion significantly decreased in the Miso group. The SBP reduction was not associated with increases in either urinary sodium excretion or fractional excretion of sodium. Conclusions: SBP reduction by very low-dose of the Miso extract may be mediated partly by mechanisms other than renal sodium handling.展开更多
BACKGROUND:Since we have previously shown an increase of mast cells in the small bowel and in the mesenteric lymph nodes in the rats with prehepatic portal hypertension,it can be hypothesized that this essential infla...BACKGROUND:Since we have previously shown an increase of mast cells in the small bowel and in the mesenteric lymph nodes in the rats with prehepatic portal hypertension,it can be hypothesized that this essential inflammatory cell would be involved in the pathogeny of the splanchnic changes related to portal hypertension. METHODS:To verify this hypothesis,we first studied mast cell infiltration in the ileum and in the mesenteric lymph nodes in sham-operated male Wistar rats(n=12) and in short-term prehepatic portal hypertensive rats (n=12),and the serum levels of rat mast cell protease Ⅱ(RMCP-Ⅱ)by ELISA.In a second set of experiments ketotifen,a mast cell stabilizer drug,was administered to sham-operated(n=10)and portal hypertensive(n=12) rats 24 hours before the intervention and prostanoids (PGE2,PGI2,TXB2)and leukotrienes(LTC4,LTB4)were assayed by RIA,mast cell infiltration in the ileum and in the mesenteric lymph nodes and the serum levels of RMCP-Ⅱwere also studied,to show its effectiveness to prevent the mesenteric alterations produced by the inflammatory mediators released by the mast cell. RESULTS:Forty-eight hours after the intervention RMCP-Ⅱ (P<0.05),PGE2(P<0.001)and LTC4 serum levels decreased and mast cell number and RMCP-Ⅱlevels increased in mesenteric lymph nodes in portal hypertensive rats.Prophylactic administration of ketotifen reduced portal pressure(P<0.001),serum levels of PGE2(P<0.001)and RMCP-Ⅱ(P<0.001)in mesenteric lymph nodes. CONCLUSIONS:In acute portal hypertension in the rat,the mast cell translocation from intestinal mucosa to mesenteric lymph nodes,where they are activated and degranulates,would represent a defence mechanism to avoid the activation of an acute and massive inflammatory response in this location.Prophylactic administration of ketotifen is able to reduce the splanchnic inflammatory changes related to acute portal hypertension in the rat.展开更多
AIM: To research the effect of erythropoietin (EPO) to the HIF-1\iNOS signal transduction path in retina in chronic ocular hypertension rat. METHODS: One hundred and twenty Wistar rats were divided into 12 groups rand...AIM: To research the effect of erythropoietin (EPO) to the HIF-1\iNOS signal transduction path in retina in chronic ocular hypertension rat. METHODS: One hundred and twenty Wistar rats were divided into 12 groups randomly. Two episcleral veins were coagulated unilaterally in rats with electric coagulator to establish the glaucoma model. PT-PCR and Western Blot analysis were used to examine the expression of Caspase-9 genes in retina. And the changes of ERG-b wave before and after were detected using EPO. RESULTS: In EPO drug treatment group, the amplitude of ERG-b wave of retina restored remarkably. There was significant difference between two groups (P< 0.05). The expression of HIF-1\iNOS mRNA and protein in EPO drug treatment group were weakened remarkably. It was statistically different compared with the non-drug treatment group. CONCLUSION: One of protect mechanisms of EPO to injured retina caused by chronic intraocular hypertension is through HIF-1\iNOS signal conduct path.展开更多
AIM: To investigate the anti-apoptotic effect of transforming growth factor beta-1 (TGF-β1) on chronic ocular hypertension. METHODS: The expression of TGF-β1 in retinal ganglion cells (RCGs) was measured using the i...AIM: To investigate the anti-apoptotic effect of transforming growth factor beta-1 (TGF-β1) on chronic ocular hypertension. METHODS: The expression of TGF-β1 in retinal ganglion cells (RCGs) was measured using the immunohistochemiscal S-P method and real-time PCR in the normally control group, the ocular hypertension group (experimental group A), the ocular hypertension plus antibody intervention group (experimental group B) and the ocular hypertension plus antigen intervention group (experimental group C) at 1, 2, 3 and 4 weeks postoperatively. The count of apoptotic RCGs was measured using the TUNEL method. RESULTS: The expression of TGF-β1 was significantly higher in experimental group C than that in other three groups (P<0.05). The expression was the lowest in experimental group B (4.17%). A statistically significant difference was noted between the four groups (P <0.01). The count of apoptotic RCGs was statistically significantly lower in experimental group C than that in the experimental groups A and B (P <0.01). A statistically significant difference was noted in the count of apoptotic RCGs between these three experimental groups (P <0.01). CONCLUSION: TGF-β1 can inhibit the apoptosis of RCGs in rats with chronic ocular hypertension.展开更多
In order to study the effect of nitric oxide (NO) on the expression of hypoxia inducible factor 1 alpha (HIF 1α) mRNA in hypoxic pulmonary hypertension (HPH) rats, 30 healthy male Wistar rats were randomly divide...In order to study the effect of nitric oxide (NO) on the expression of hypoxia inducible factor 1 alpha (HIF 1α) mRNA in hypoxic pulmonary hypertension (HPH) rats, 30 healthy male Wistar rats were randomly divided into normoxic control group, chronic hypoxic group and hypoxia plus L argine (L Arg) group. The animal model of HPH was developed. The mean pulmonary arterial pressure (mPAP) was measured by inserting a microcatheter into the pulmonary artery. The HIF 1α mRNA expression levels were detected by in situ hybridization (ISH) and semiquantitative RT PCR. It was found that after 14 days hypoxia, the mPAP in normoxic control group (17.6±2 7 mmHg,1 mmHg=0 133 kPa) was significantly lower than that in chronic hypoxic group(35.8±6.1 mmHg, t =0.2918, P <0.05) and mPAP in chronic hypoxic group was higher than that in hypoxia plus L argine group(24.4±3.8 mmHg, t =0.2563, P <0.05). ISH showed that the expression of HIF 1α mRNA in the intraacinar pulmonary arteriolae (IAPA) in normoxic control group (0.1076±0.0205) was markedly weaker than that in chronic hypoxic group (0.3317±0.0683, t =3.125, P <0.05) and that in chronic hypoxic group was stronger than that in hypoxia plus L argine group (0.1928±0.0381, t =2.844, P <0.05). RT PCR showed that the content of HIF 1α mRNA in chronic hypoxic group (2.5395±0.6449) was 2.16 times and 1.75 times higher than that in normoxic control group (1.1781±0.3628) and hypoxia plus L argine group (1.4511±0.3981), respectively. It is concluded that NO can reduce the mPAP by the inhibition of the expression of HIF 1α mRNA, which may be one of the mechanisms through which NO affects the pathogenesis of HPH.展开更多
AIM: To explore the effect of the Notch signaling pathway on retinal ganglion cells(RGCs) and optic nerve in rats with acute ocular hypertension(OH).METHODS: Totally 48 Sprague-Dawley(SD) rats were included, a...AIM: To explore the effect of the Notch signaling pathway on retinal ganglion cells(RGCs) and optic nerve in rats with acute ocular hypertension(OH).METHODS: Totally 48 Sprague-Dawley(SD) rats were included, among which 36 rats were selected to establish acute OH models. OH rats received a single intravitreal injection of 2 μL phosphate buffered solution(PBS) and another group of OH rats received a single intravitreal injection of 10 μmol/L γ-secretase inhibitor(DAPT). Quantitative real-time polymerase chain reaction(qPCR) and Western blot assay were adopted to determine the mRNA level of Notch and the protein levels of Notch, Bcl-2, Bax, caspase-3, and growth-associated protein 43(GAP-43). The RGC apoptosis conditions were assessed by TUNEL staining.RESULTS: The OH rats and PBS-injected rats had increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, with severer macular edema and RGCs more loosely aligned, when compared with the normal rats. The DAPT-treated rats displayed increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, in comparison with the OH rats and PBSinjected rats. RGCs were hardly observed and macular edema became severe in the DAPT-treated rat.CONCLUSION: The Notch signaling pathway may suppress the apoptosis of retinal ganglion cells and enhances the regeneration of the damaged optic nerves in rats with acute OH.展开更多
To observe changes in activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in rats with monocrotaline-induced pulmonary hypertension. Methods: Adult ma1e Sprague-Dawley rats were given a single ...To observe changes in activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in rats with monocrotaline-induced pulmonary hypertension. Methods: Adult ma1e Sprague-Dawley rats were given a single subcutaneous injection of monocrotaline (MCT, 60 mg/kg) for modeling PH. Activities of SOD and contents of MDA in plasma and pulmonary homogenate were measured by colorimetric analysis. The thickness of the media of pulmonary arterioles (external diameter <100μm) was measured using colour image analysis system. Results: Four weeks after injection of MCT, activities of SOD in venous plasma and pulmonary homogenate for MCT group were 106±45 NU/ml (P<0.05) and 317±59 NU/ml (P<0.01) respectively, whileactivities of SOD for control group were 159±28 NU/ml (P<0.05) and 505±47 NU/ml (P<0.01) respectively.COntents of MDA in venous plasma and pulmonary homogenate for MCT group were 15±5 and 59±14 μmol/L,while contents of MDA for control group were 5. 3±2. 8 and 32±19 ±mol/L. The thickness of the media of pulmonary arterioles increased significantly. Conclusion: The primary cause of PH is the injury of pulmonary vascular endothelial cells by MCT, which decreases the O2 removing ability of the lungs but increases lipid peroxidation,thus inducing PH.展开更多
In this study, effects of hot water extract of Paecilomyces hepiali mycelia on hypertension parameters in spontaneously hypertensive rats (SHR) were investigated. The tested parameters included blood pressure, blood a...In this study, effects of hot water extract of Paecilomyces hepiali mycelia on hypertension parameters in spontaneously hypertensive rats (SHR) were investigated. The tested parameters included blood pressure, blood and urine biochemical composition, renin and angiotensin II levels in the blood. Prior to these tests, the extract was examined for toxicity. The fungus was cultivated in a solid medium composed of 40 g brown rice, 0.32 g glucose, 0.65 g sucrose, 2 g peptone and 65 ml corn steep liquor. No abnormality or harmful effects were observed in the toxicity test. Administration of a continuous-dose, once daily, to SHR for 27 weeks (from 13 weeks of age) decreased the systolic blood pressure (SBP) significantly. Levels of blood urea nitrogen, β-lipoprotein lipid peroxides and low density lipoprotein were significantly lower in the treated groups when compared to the control group. Urinary protein was significantly reduced in the middle and high dose groups. In comparison with the control group (0 mg/kg/10ml/day), significantly higher values were obtained for total cholesterol in groups that were given middle (170 mg/kg/10ml/day) and high (250 mg/kg/10ml/day) dosages. In all dosages (low, middle and high) the values for triglyceride were significantly higher than value found in the control group. In terms of angiotensin II levels, the value in the control group was markedly higher than values in the other groups. The results suggest that oral administration of hot water extract of P. hepiali mycelia has ability to control hypertension in rats.展开更多
Objective\ To investigate expression of inositol 1,4,5 trisphosphate receptor (IP\-3R) mRNA on sacroplasmic reticular in myocardium of spontaneous hypertension rats (SHRs) and cultured vascular smooth muscle cells (V...Objective\ To investigate expression of inositol 1,4,5 trisphosphate receptor (IP\-3R) mRNA on sacroplasmic reticular in myocardium of spontaneous hypertension rats (SHRs) and cultured vascular smooth muscle cells (VSMC) of rats and effects of perindopril and urapidil on them. Methods\ SHRs were orally given perindopril (1.0 mg·kg\+\{ 1\}·d\+\{ 1\}) or urapidil (15 mg·kg\+\{ 1\}·d\+\{ 1\}) for 24 weeks, respectively. Expression of IP\-3R mRNA was examined by semi quantitative reverse transcription polymers chain reaction (RT PCR) using three oligonuclotide primers for each subtype of IP\-3R with β actin as internal label. Results\ All subtypes of IP\-3R were expressed in myocardium of SHR, WKY and cultured VSMC. Expression of IP\-3R mRNA in left ventricle of SHR was markedly enhanced. Urapidil could down regulate expression of IP\-3R Ⅰand IP\-3R Ⅲ, perindopril slightly increased expression of IP\-3R Ⅱ and decreased expression of IP\-3R Ⅰand IP\-3R Ⅲ in myocardium of SHR. Conclusion\ Our results suggest that expression of IP\-3R mRNA in cardiovascular system could be regulated by urapidil and perindopril.展开更多
BACKGROUND: Hyperbaric oxygen (HBO) is used for treating glaucoma, and affirmative curative effect has been obtained. HBO can sensitively reflect the obviously heightened b wave of electroretinogram (ERG) of inju...BACKGROUND: Hyperbaric oxygen (HBO) is used for treating glaucoma, and affirmative curative effect has been obtained. HBO can sensitively reflect the obviously heightened b wave of electroretinogram (ERG) of injured tissue. OBJECTIVE: To observe the effect of HBO treatment on retinal function of rats with acute experimental intraocular hypertension with ERG. DESIGN: Randomized controlled experiment. SETTING: Department of Ophthalmology, Third Xiangya Hospital, Central South University; Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University; Department of Anatomy, Xiangya Hospital, Central South University. MATERIALS: Eighteen adult healthy Wistar rats, of either gender, weighing from 150 to 250 g, were provided by the Animal Room of Central South University. Type YLCO. 5/I A baby hyperbaric oxygen chamber, type LMS-2A two-channel physiological recorder, type BG-1 retina exposure system, Jiangwan type Ⅰ stereotaxis instrument. METHODS: This experiment was carried out in the Central South University between March and September 2006. Eighteen healthy Wistar rats were made into models of acute experimental intraocular hypertension. Then, they were divided into two groups: model group and HBO treatment group, with 9 in each group. Following 7 days of HBO treatment, the rats in HBO treatment group were placed in Type YLCO. 5/I A baby hyperbaric oxygen chamber, which was pressurized with pure oxygen( volume fraction 0.825 ± 0.025).The treatment pressure was 0.2 MPa. The rats in HBO treatment group daily inhaled HBO for 80 minutes within 7 days; Rats in the model group were untouched. The performance of eyes was observed under the status of intraocular hypertension. ERG was recorded before, during and 7 days after modeling, meanwhile, the recovery rate of b wave from ERG was calculated. Recovery rate of b wave from ERG=(amplitude orb wave 7 days after modeling/amplitude orb wave before modeling)× 100%. MAIN OUTCOME MEASURES: ①Performance of eyes under the status of intraocular hypertension. ②Recovery rate orb wave of ERG. RESULTS: All the 18 rats were involved in the final analysis. ①Performance of eyes under the status of intmocular hypertension.: When intraocular pressure increased until b wave of ERG disappeared, two eyes of rats with corneal opacity, dilated pupils, pale iris and stiffened eyeballs were found. ②Recovery rate of b wave of ERG in the HBO treatment group was significantly higher than that in the model group [(60.04±19.33)% vs. (41.85 ± 13.20)%, t =3.298, P 〈 0,01]. CONCLUSION: HBO treatment can obviously promote the recovery of retinal function following acute intraocular hypertension.展开更多
Angiotension-Ⅱ(A-Ⅱ) receptor maximal binding capacity (Bmax) and dissociation constants (Kd) of different blood vessels in rats with prehepatic portal hypertension were studied by radioligand binding analysis. The r...Angiotension-Ⅱ(A-Ⅱ) receptor maximal binding capacity (Bmax) and dissociation constants (Kd) of different blood vessels in rats with prehepatic portal hypertension were studied by radioligand binding analysis. The results showed that the A-Ⅱreceptor Bmax. in the thoracic aorta, superior mesenteric artery and portal vein of portal hypertensive animals (113. 7±19. 4 fmol/mg protein, 206.9 ±39. 3 fmol/mg protein and 31. 5±9. 2 fmol/mg protein respectively ) was all significantly lower than that of controls (146. 8±24. 5 fmol/mg protein, 297. 2±44. 7 fmol/mg protein and 53. 4±12.1 fmol/mg protein respectively, P<0. 01).The A-Ⅱ receptor Kd in the superior mesenteric artery was markedly increased in portal hypertensive animals (1. 03±0.11 nmol/L) compared with that in controls (0. 88±0. 08 nmol/L, P<0. 05). In the thoracic aorta and portal vein, the A-Ⅱ receptor Kd in portal hypertensive animals was slightly higher than that in controls, but no significant difference was observed between the two groups. The results suggested that the vascular hyporesponsiveness to A-Ⅱ in portal hypertension was caused partially by a reduction in number and a decrease in affinity of vascular A- Ⅱ receptors, and these changes might possibly lead to the formation of hyperdynamic circulation.展开更多
Objective: To explore the mechanism of Chuanxiong in alleviating hypoxic pulmonary hypertension in rats by inhibiting pulmonary vascular remodeling. Methods: Thirty healthy and clean male SD rats weighing (180 - 220) ...Objective: To explore the mechanism of Chuanxiong in alleviating hypoxic pulmonary hypertension in rats by inhibiting pulmonary vascular remodeling. Methods: Thirty healthy and clean male SD rats weighing (180 - 220) g were randomly divided into three groups (n = 10): normoxia group (n), hypoxia group (H) and Chuanxiong group (L). Group N was fed in normoxic environment, and the other two groups were fed in hypoxic (9% 11% O2) environment for 4 weeks, 8 h/D, 6 days a week. Rats in group L were gavaged with Ligusticum chuanxiong solution diluted with normal saline at the concentration of 300 mg/kg, and rats in group H were gavaged with equal volume of normal saline. After 4 weeks, the mean pulmonary artery pressure was measured. After pulmonary perfusion, the right ventricular free wall and left ventricle plus ventricular septum were taken to measure the right ventricular hypertrophy index. The changes of pulmonary morphology and ultrastructure were observed under light microscope. Results: Compared with group n, the average pulmonary artery pressure and right ventricular hypertrophy index in the other two groups increased, and the thickening of pulmonary vascular wall was obvious under microscope (P Conclusion: Ligusticum chuanxiong can relieve pulmonary artery pressure in rats by inhibiting pulmonary vascular remodeling.展开更多
文摘Objective: This study is to observe the effects of Salvia miltiorrhiza injection on blood pressure and cardiac function in rats with pregnancy-induced hypertension and preeclampsia. Methodology: Syncytiotrophoblast microvilli (stbm) and l-arginine nitrosyl methyl ester were screened out via caudal vein injection. Twenty gestational hypertension-preeclampsia model SD (Sprague Dawley) rats successfully induced by L-NAME (L-arginine Nitrosyl methyl ester) were randomly divided into 2 groups (model group and Danshen injection group, n = 10). Then another 10 normal pregnant SD rats without model were selected as blank control group. The Salvia miltiorrhiza injection group was given Salvia miltiorrhiza injection (0.5 g?kg?1?d?1) through tail vein, and the control group and model group were given equal volume of normal saline through tail vein injection. All three groups were treated by tail vein injection once a day (d) for 7 days. After treatment, heart rate (HR), Systolic pressure (SP), diastolic pressure (DP) and mean arterial pressure (MAP) were measured by tail artery. Left ventricular end-diastolic diameter (LVDd) and Left ventricular end systolic diameter (LVDs) were recorded by echocardiography. Left ventricular end diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), left ventricular ejection fraction (left ventricular ejection) fraction, LVEF) and the maximum rate of increase/decrease of left ventricular pressure during isovolemic systole (+dp/dtmax/?dp/dtmax);Endothelin-1 (ET-1) levels in rat tail vein blood were detected by ELISA. Results: SP, DP, MP, HR, LVSP, LVDs and ?dp/dtmaxx were all decreased, plasma ET-1 expression was low, and LVDd, LVEDP, LVEF, and +dp/dtmax were all increased in the Salvia miltiorroot injection group, with statistical significance compared to the model group (p Conclusion: Salvia miltiorrhiza injection can improve the cardiac function and reduce blood pressure in rats with pregnancy-induced hypertension and preeclampsia, and the mechanism may be related to alleviating systemic arteriolar spasm by regulating ET-1 level.
文摘Hypertension and metabolic syndrome, both of which increase with age, are multifactorial disorders. Their etiology is complex, making it challenging to isolate involved genes. This study aimed to characterize the hepatic gene expression in spontaneously hypertensive rats (SHR) at different ages. Blood pressure in SHR was determined by tail-cuff method at one and three months of age. Hepatic RNA was isolated and gene expression was compared using microarrays. Comparison between SHR and normotensive rats revealed significant variation in gene expression: 98 genes were upregulated and 122 were downregulated in SHR;while 88 genes were upregulated and 139 genes were downregulated in age-matched normotensive rats. Furthermore, within the SHR group, 110 genes were found to be upregulated and 168 genes downregulated across different ages. Analyses via the Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways revealed that several genes are potentially implicated in both, hypertension and metabolic syndrome. The results suggest that SHR display variations in gene expression due to aging, and when compared to normotensive rats. These variations could contribute to the development of hypertension and metabolic syndrome. Microarray studies involving older rats are necessary to further validate these findings.
文摘Objective:To study the influence of bone marrow mesenchymal stem cells(MSCs)transplantation on hypoxic pulmonary hypertension(HPH)in rats.Methods:MSCs in SD rats were separated,cultivated,identified in vitro,and labeled by the green fluorescence protein(GFP)adenovirus.Healthy male SD rats were randomly divided into four groups:normal control group(NC group)and HPH group,with eight rats in each group respectively;HPH+mesenchymal stem cell transplantation group(MSCs group)and HPH+vascular endothelial growth factor+mesenchymal stem cell transplantation group(VEGF+MSCs group),with twenty-four rats in each group respectively.In this experiment,intermittent normobaric hypoxia was employed to establish the pulmonary hypertension rat models,with stem cells transfected and transplanted.The mean pulmonary artery pressure(mPAP)was observed in rats to calculate the right ventricular hypertrophy index(RVHI);the morphological changes of pulmonary arterioles in each group of rats were observed under the microscope;the distribution and manifestation of MSCs fluorescently labeled by adenovirus transfection were observed in pulmonary arterioles under the fluorescence microscope at the set time points of 7 d,14 d and 28 d after the transplantation of stem cells.Results:For NC group,the mPAP(mmHg)was 15.5±1.5 at 28 d,while the mPAP in HPH,MSCs and VEGF+MSCs groups were 26.1±1.9,21.6±2.7 and 20.1±2.9 respectively which were apparently higher than that in NC group(p<.01).Compared with HPH group(p<.01),the mPAP was obviously decreased in MSCs and VEGF+MSCs groups.There was no significant difference between MSCs and VEGF+MSCs groups.At 28 d,RVHI for NC group was 0.28±0.02,while the RVHI in HPH,MSCs and VEGF+MSCs groups were 0.43±0.07,0.34±0.03 and 0.35±0.01 respectively which were apparently higher than that in NC group(p<.01).In comparison with HPH group,RVHI was significantly decreased in MSCs and VEGF+MSCs groups(p<.05).There was no significant difference between MSCs and VEGF+MSCs groups.For HPH group,at 28 d,pulmonary arterioles were apparently thickened,with luminal stenosis&obliteration and incomplete endothelial cells.Compared with HPH group,pulmonary arterioles in MSCs group became thinning,with the lumen unobstructed and the integrity of endothelial cells improved.The changes in the manifestation of MSCs and VEGF+MSCs groups were not significant.Conclusions:The transplantation of MSCs can improve the remodeling of pulmonary arterioles to partially reverse the progress of HPH;the combined transplantation of VEGF and MSCs doesn’t improve the effect of MSC transplantation.
基金This study was supported by a grant from the Key Basic Research Program of Shanghai (No.014119067).
文摘BACKGROUND : The importance of nitric oxide (NO) in the pathogenesis of portal hypertension (PHT) has been extensively studied, but whether or not prostacyclin (PGI2) plays a role in formation and development of hyperdynamic circutatory state in PHT has not been verified. The present study was undertaken to investigate the possible interaction between prostacyclin (PGI2) and nitric oxide (NO) in the hyperdynamic circulatory state of rats with chronic portal hypertension (PHT), by measuring the hemodynamic changes and expression of cyclooxygenase (COX) mRNA in vessels and small intestine after administration of Nω- nitro-L-arginine (L-NNA) or indomethacin (INDO) either in the short-term (7 days) or long-term (15 days). METHODS: Ninety-seven male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) induced by injection of CCl4, prehepatic portal hypertension (PHPH) induced by partial stenosis of the portal vein, and sham-operated controls (SO). Animals of each group received L-NNA or INDO either for 7 or 15 days, with saline as control. Splanchnic hemodynamics was measured by the radioactive microsphere technique. The concentration of NO in serum was determined as the nitrate; nitrite ratio (NO2-/NO3-, μmol/L) by a colorometric method, and that of PGI2 was measured by specific radioimmunoassay for its stable hydrolysis product 6-keto-PGF1α (pg/ml). The reverse transcription- polymerase chain reaction measured the levels of COX-1 mRNA in the superior mesenteric artery, thoracic aorta, and small intestine of these rats.RESULTS: Compared with SO rats, COX-1 mRNA expression and the concentrations of plasma 6-keto- PGF1α and serum NO2-/NO3- were enhanced in both IHPH and PHPH rats; splanchnic vascular resistance (SVR) decreased, but portal venous inflow (PVI) markedly increased (P<0.05). Seven or 15 days of L-NNA treatment reduced COX-1 mRNA expression in these vessels and the small intestine, concomitant with a significant decrease in the concentration of plasma PGI2 and serum NO in IHPH and PHPH rats (P<0.05). At the same time, PVI decreased but SVR increased significantly (P<0.05). In both IHPH and PHPH rats, the COX-1 mRNA expression and the concentration of plasma PGI2 after No synthase (NOS) blockade for 15 days were higher than those for 7 days, whereas the hyperdynamic circulatory state was improved after NOS blockade for 15 days compared with 7 days. The concentration of PGI2 treated by INDO for 15 days was not significantly different from that after 7-day COX blockade, and hemodynamics restored hyperdynamic circulatory state. CONCLUSIONS: The hyperdynamic circulatory state in rats with PHT is correlated with the concentration of serum NO. There is a possible interaction between PGI2 and NO in the hyperhemodynamics of PHT. PGI2 is probably not the mediator in the formation and development of the hyperdynamic circulatory state in rats with chronic PHT.
文摘Intravenous and intratracheal implantation of mesenchymal stem cells (MSCs) may offer ameliorating effects on pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. The aim of this study was to examine the anti-remodeling effect of intravenous MSCs (VMSCs) and intratracheal MSCs (TMSCs) in rats with PH, and the underlying mechanisms. MSCs were isolated from rat bone marrow and cultured. PH was induced in rats by intraperitoneal injection of MCT. One week after MCT administration, the rats were divided into 3 groups in terms of different treatments: VMSCs group (intravenous injection of MSCs), TMSCs group (intratracheal injection of MSCs), PH group (no treatment given). Those receiving saline instead of MCT served as negative control (control group). Pulmonary arterial structure was pathologically observed, pulmonary arterial dynamics measured, and remodeling-associated cytokines Smad2 and Smad3 detected in the lungs, three weeks after MCT injection. The results showed that PH group versus control group had higher pulmonary arterial pressure (PAP) and wall thickness index (WTI) 21 days after MCT treatment. The expression of phosphorylated (p)-Smad2 and the ratio of p-Smad2/Smad2 were much higher in PH group than in control group. Fluorescence-labeled MSCs were extensively distributed in rats’ lungs in VMSCs and TMSCs groups 3 and 14 days after transplantation, but not found in the media of the pulmonary artery. WTI and PAP were significantly lower in both VMSCs and TMSCs groups than in PH group three weeks after MCT injection. The p-Smad2 expression and the ratio of p-Smad2/Smad2 were obviously reduced in VMSCs and TMSCs groups as compared with those in PH group. In conclusion, both intravenous and intratracheal transplantation of MSCs can attenuate PAP and pulmonary artery remodeling in MCT-induced PH rats, which may be associated with the early suppression of Smad2 phosphorylation via paracrine pathways.
基金Foundation:Directorate General of Higher Education(DGHE),National Education Ministry Republic of Indonesia
文摘AIM: To evaluate effect of hypertension on retinal ganglion cell(RGC) apoptosis, intraocular pressure(IOP),and the activation of endothelin-1(ET-1) signaling pathway in central retinal artery(CRA) in rats.METHODS: The experimental study was performed on20 male Sprague Dawley rats that were divided into control group, and hypertension groups. The hypertension was induced by subcutaneous deoxycorticoacetate(DOCA)10 mg/kg twice a week and administered 0.9% Na Cl solution daily for 2, 6, and 10 wk. Blood pressure(BP) was measured using animal BP analyzer. IOP was measured by handheld tonometry. Retinal tissue preparations by paraffin blocks were made after enucleation. The expression of ET-1, e NOS, ET-1 receptor A(ETRA), ET-1receptor B(ETRB), and phosphorylated myosin light chain kinase(MLCK), and caldesmon(Ca D) in CRA and RGC apoptosis were evaluated through immunofluorescent staining method then observed using laser scanning confocal microscopy. RESULTS: BP significantly increased in all of the hypertension groups compared to control(P =0.001).Peak IOP elevation(7.78±4.14 mm Hg) and RGC apoptosis(576.15±33.28 Au) occurred on 2wk of hypertension. ET-1expression(1238.6±55.1 Au) and e NOS expression(2814.2±70.7 Au) were found highest in 2wk of hypertension,although the ratio of ET-1/e NOS decreased since 2wk.ETRAreached peak expression in 10 wk of hypertension(1219.4 ±6.3 Au), while ETRBsignificantly increased only in 2 weeks group(1069.2 ±9.6 Au). The highest MLCK expression(1190.09±58.32 Au), Ca D(1670.28±18.36 Au)were also found in 2wk of hypertension.CONCLUSION: Hypertension effects to activation of ET-1 signaling pathway significantly in CRA, elevation of IOP, and RGC apoptosis. The highest value was achieved at 2wk, which is the development phase of hypertension.
文摘Pulmonary arterial hypertension (PAH) is a progressive disease associated with increased constriction and remodeling of the pulmonary vasculature. Quercetin is a natural fiavonoid and has a variety of pharmacological effects including improvement of endothelial cell function. However, its pharmacological effects on pulmonary hypertension have been rarely reported. We sought to observe the protective effect of quercetin in rats with monocrotaline induced PAH. We divided 30 male Sprague-Dawley rats randomly into three groups with ten rats in each group: the monocrotaline group, the quercetin group and the control group. We found that, compared with the controls, the mean pulmonary artery pressure (mPAP) and the right ventricular hypertrophy index in the monocrotaline group were significantly higher (P 〈 0.01). Quercetin caused a significant reduction both in the mPAP and fight ventricular hypertrophy index compared with the monocrotaline group (P 〈 0.01) while no difference was found between the quercefin group and the control group (P 〉 0.05). Monocrotaline induced a marked increase in the wall thickness (WT) in small and mid-sized pulmonary arteries compared with the controls (P 〈 0.01). Monocrotaline also induced a marked increase in the wall area (WA) in small [(56.38 ±6.65)% in monocrotaline vs. (19.80±4.63)% in control] and mid-sized [(43.71± 5.38)% in monocrotaline vs. (14.24± 3.66)% in control] pulmonary arteries (P 〈 0.01). Quercefin treatment markedly reduced monocrotaline induced increase in both WT and WA (P 〈 0.01), which, however, still remained significantly elevated compared with those of the controls (P 〈 0.01). Furthermore, compared with controls, proliferating cell nuclear antigen (PCNA) expression in the pulmonary artery tissues was markedly increased by monocrotaline [(45.59± 1.27) in monocrotaline vs. (9.64± 0.69) in controls], which was significantly attenuated by quercetin. Our animal experiment indicated that quercetin could have protective effects on monocrotaline-induced PAH.
文摘Objective: Long-term intake of Miso attenuates hypertension in Dahl salt-sensitive (Dahl S) rats through an increased urinary sodium excretion. We examined whether a bolus injection into the peritoneal cavity (i.p.) or a continuous subcutaneous infusion of a Miso extract attenuates hypertension in Dahl S rats. Materials and Methods: We investigated the effects of a bolus, i.p. injection of 50 mg Miso extract in 0.5 mL on hypertension in Dahl S rats, and examined whether a long-term subcutaneous infusion of the Miso extract (50 mg Miso/day), using an osmotic mini-pump working for 14 days, attenuates hypertension in Dahl S rats. Results: A bolus, i.p. injection of 50 mg Miso extract decreased SBP in 2 hrs. The reduction was significant at 4 hrs, and SBP returned to the baseline at 24 hrs. The SBP reduction at 4 hrs after the injection was increasingly greater each day during the 4 days. The SBP reduction by the Miso extract was dose-dependent and the antihy-pertensive activity occurs in a <5 kDa fraction of the extract. The subcutaneous infusion of 50 mg Miso extract/day for 14 days significantly attenuated hypertension in Dahl S rats. The SBP reduction was associated with significant decreases in the heart and kidney weights. Urinary protein excretion significantly decreased in the Miso group. The SBP reduction was not associated with increases in either urinary sodium excretion or fractional excretion of sodium. Conclusions: SBP reduction by very low-dose of the Miso extract may be mediated partly by mechanisms other than renal sodium handling.
基金grants from the Department of Health.Castilla-La Mancha Regional Council(Ref.04047-00 and PI-2007/64).Ketotifen was kindly provided by Novartis(Barcelona,Spain).
文摘BACKGROUND:Since we have previously shown an increase of mast cells in the small bowel and in the mesenteric lymph nodes in the rats with prehepatic portal hypertension,it can be hypothesized that this essential inflammatory cell would be involved in the pathogeny of the splanchnic changes related to portal hypertension. METHODS:To verify this hypothesis,we first studied mast cell infiltration in the ileum and in the mesenteric lymph nodes in sham-operated male Wistar rats(n=12) and in short-term prehepatic portal hypertensive rats (n=12),and the serum levels of rat mast cell protease Ⅱ(RMCP-Ⅱ)by ELISA.In a second set of experiments ketotifen,a mast cell stabilizer drug,was administered to sham-operated(n=10)and portal hypertensive(n=12) rats 24 hours before the intervention and prostanoids (PGE2,PGI2,TXB2)and leukotrienes(LTC4,LTB4)were assayed by RIA,mast cell infiltration in the ileum and in the mesenteric lymph nodes and the serum levels of RMCP-Ⅱwere also studied,to show its effectiveness to prevent the mesenteric alterations produced by the inflammatory mediators released by the mast cell. RESULTS:Forty-eight hours after the intervention RMCP-Ⅱ (P<0.05),PGE2(P<0.001)and LTC4 serum levels decreased and mast cell number and RMCP-Ⅱlevels increased in mesenteric lymph nodes in portal hypertensive rats.Prophylactic administration of ketotifen reduced portal pressure(P<0.001),serum levels of PGE2(P<0.001)and RMCP-Ⅱ(P<0.001)in mesenteric lymph nodes. CONCLUSIONS:In acute portal hypertension in the rat,the mast cell translocation from intestinal mucosa to mesenteric lymph nodes,where they are activated and degranulates,would represent a defence mechanism to avoid the activation of an acute and massive inflammatory response in this location.Prophylactic administration of ketotifen is able to reduce the splanchnic inflammatory changes related to acute portal hypertension in the rat.
文摘AIM: To research the effect of erythropoietin (EPO) to the HIF-1\iNOS signal transduction path in retina in chronic ocular hypertension rat. METHODS: One hundred and twenty Wistar rats were divided into 12 groups randomly. Two episcleral veins were coagulated unilaterally in rats with electric coagulator to establish the glaucoma model. PT-PCR and Western Blot analysis were used to examine the expression of Caspase-9 genes in retina. And the changes of ERG-b wave before and after were detected using EPO. RESULTS: In EPO drug treatment group, the amplitude of ERG-b wave of retina restored remarkably. There was significant difference between two groups (P< 0.05). The expression of HIF-1\iNOS mRNA and protein in EPO drug treatment group were weakened remarkably. It was statistically different compared with the non-drug treatment group. CONCLUSION: One of protect mechanisms of EPO to injured retina caused by chronic intraocular hypertension is through HIF-1\iNOS signal conduct path.
文摘AIM: To investigate the anti-apoptotic effect of transforming growth factor beta-1 (TGF-β1) on chronic ocular hypertension. METHODS: The expression of TGF-β1 in retinal ganglion cells (RCGs) was measured using the immunohistochemiscal S-P method and real-time PCR in the normally control group, the ocular hypertension group (experimental group A), the ocular hypertension plus antibody intervention group (experimental group B) and the ocular hypertension plus antigen intervention group (experimental group C) at 1, 2, 3 and 4 weeks postoperatively. The count of apoptotic RCGs was measured using the TUNEL method. RESULTS: The expression of TGF-β1 was significantly higher in experimental group C than that in other three groups (P<0.05). The expression was the lowest in experimental group B (4.17%). A statistically significant difference was noted between the four groups (P <0.01). The count of apoptotic RCGs was statistically significantly lower in experimental group C than that in the experimental groups A and B (P <0.01). A statistically significant difference was noted in the count of apoptotic RCGs between these three experimental groups (P <0.01). CONCLUSION: TGF-β1 can inhibit the apoptosis of RCGs in rats with chronic ocular hypertension.
文摘In order to study the effect of nitric oxide (NO) on the expression of hypoxia inducible factor 1 alpha (HIF 1α) mRNA in hypoxic pulmonary hypertension (HPH) rats, 30 healthy male Wistar rats were randomly divided into normoxic control group, chronic hypoxic group and hypoxia plus L argine (L Arg) group. The animal model of HPH was developed. The mean pulmonary arterial pressure (mPAP) was measured by inserting a microcatheter into the pulmonary artery. The HIF 1α mRNA expression levels were detected by in situ hybridization (ISH) and semiquantitative RT PCR. It was found that after 14 days hypoxia, the mPAP in normoxic control group (17.6±2 7 mmHg,1 mmHg=0 133 kPa) was significantly lower than that in chronic hypoxic group(35.8±6.1 mmHg, t =0.2918, P <0.05) and mPAP in chronic hypoxic group was higher than that in hypoxia plus L argine group(24.4±3.8 mmHg, t =0.2563, P <0.05). ISH showed that the expression of HIF 1α mRNA in the intraacinar pulmonary arteriolae (IAPA) in normoxic control group (0.1076±0.0205) was markedly weaker than that in chronic hypoxic group (0.3317±0.0683, t =3.125, P <0.05) and that in chronic hypoxic group was stronger than that in hypoxia plus L argine group (0.1928±0.0381, t =2.844, P <0.05). RT PCR showed that the content of HIF 1α mRNA in chronic hypoxic group (2.5395±0.6449) was 2.16 times and 1.75 times higher than that in normoxic control group (1.1781±0.3628) and hypoxia plus L argine group (1.4511±0.3981), respectively. It is concluded that NO can reduce the mPAP by the inhibition of the expression of HIF 1α mRNA, which may be one of the mechanisms through which NO affects the pathogenesis of HPH.
基金Supported by Fund of Hainan Provincial Health Department(No.1601032037A2001)
文摘AIM: To explore the effect of the Notch signaling pathway on retinal ganglion cells(RGCs) and optic nerve in rats with acute ocular hypertension(OH).METHODS: Totally 48 Sprague-Dawley(SD) rats were included, among which 36 rats were selected to establish acute OH models. OH rats received a single intravitreal injection of 2 μL phosphate buffered solution(PBS) and another group of OH rats received a single intravitreal injection of 10 μmol/L γ-secretase inhibitor(DAPT). Quantitative real-time polymerase chain reaction(qPCR) and Western blot assay were adopted to determine the mRNA level of Notch and the protein levels of Notch, Bcl-2, Bax, caspase-3, and growth-associated protein 43(GAP-43). The RGC apoptosis conditions were assessed by TUNEL staining.RESULTS: The OH rats and PBS-injected rats had increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, with severer macular edema and RGCs more loosely aligned, when compared with the normal rats. The DAPT-treated rats displayed increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, in comparison with the OH rats and PBSinjected rats. RGCs were hardly observed and macular edema became severe in the DAPT-treated rat.CONCLUSION: The Notch signaling pathway may suppress the apoptosis of retinal ganglion cells and enhances the regeneration of the damaged optic nerves in rats with acute OH.
文摘To observe changes in activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in rats with monocrotaline-induced pulmonary hypertension. Methods: Adult ma1e Sprague-Dawley rats were given a single subcutaneous injection of monocrotaline (MCT, 60 mg/kg) for modeling PH. Activities of SOD and contents of MDA in plasma and pulmonary homogenate were measured by colorimetric analysis. The thickness of the media of pulmonary arterioles (external diameter <100μm) was measured using colour image analysis system. Results: Four weeks after injection of MCT, activities of SOD in venous plasma and pulmonary homogenate for MCT group were 106±45 NU/ml (P<0.05) and 317±59 NU/ml (P<0.01) respectively, whileactivities of SOD for control group were 159±28 NU/ml (P<0.05) and 505±47 NU/ml (P<0.01) respectively.COntents of MDA in venous plasma and pulmonary homogenate for MCT group were 15±5 and 59±14 μmol/L,while contents of MDA for control group were 5. 3±2. 8 and 32±19 ±mol/L. The thickness of the media of pulmonary arterioles increased significantly. Conclusion: The primary cause of PH is the injury of pulmonary vascular endothelial cells by MCT, which decreases the O2 removing ability of the lungs but increases lipid peroxidation,thus inducing PH.
文摘In this study, effects of hot water extract of Paecilomyces hepiali mycelia on hypertension parameters in spontaneously hypertensive rats (SHR) were investigated. The tested parameters included blood pressure, blood and urine biochemical composition, renin and angiotensin II levels in the blood. Prior to these tests, the extract was examined for toxicity. The fungus was cultivated in a solid medium composed of 40 g brown rice, 0.32 g glucose, 0.65 g sucrose, 2 g peptone and 65 ml corn steep liquor. No abnormality or harmful effects were observed in the toxicity test. Administration of a continuous-dose, once daily, to SHR for 27 weeks (from 13 weeks of age) decreased the systolic blood pressure (SBP) significantly. Levels of blood urea nitrogen, β-lipoprotein lipid peroxides and low density lipoprotein were significantly lower in the treated groups when compared to the control group. Urinary protein was significantly reduced in the middle and high dose groups. In comparison with the control group (0 mg/kg/10ml/day), significantly higher values were obtained for total cholesterol in groups that were given middle (170 mg/kg/10ml/day) and high (250 mg/kg/10ml/day) dosages. In all dosages (low, middle and high) the values for triglyceride were significantly higher than value found in the control group. In terms of angiotensin II levels, the value in the control group was markedly higher than values in the other groups. The results suggest that oral administration of hot water extract of P. hepiali mycelia has ability to control hypertension in rats.
文摘Objective\ To investigate expression of inositol 1,4,5 trisphosphate receptor (IP\-3R) mRNA on sacroplasmic reticular in myocardium of spontaneous hypertension rats (SHRs) and cultured vascular smooth muscle cells (VSMC) of rats and effects of perindopril and urapidil on them. Methods\ SHRs were orally given perindopril (1.0 mg·kg\+\{ 1\}·d\+\{ 1\}) or urapidil (15 mg·kg\+\{ 1\}·d\+\{ 1\}) for 24 weeks, respectively. Expression of IP\-3R mRNA was examined by semi quantitative reverse transcription polymers chain reaction (RT PCR) using three oligonuclotide primers for each subtype of IP\-3R with β actin as internal label. Results\ All subtypes of IP\-3R were expressed in myocardium of SHR, WKY and cultured VSMC. Expression of IP\-3R mRNA in left ventricle of SHR was markedly enhanced. Urapidil could down regulate expression of IP\-3R Ⅰand IP\-3R Ⅲ, perindopril slightly increased expression of IP\-3R Ⅱ and decreased expression of IP\-3R Ⅰand IP\-3R Ⅲ in myocardium of SHR. Conclusion\ Our results suggest that expression of IP\-3R mRNA in cardiovascular system could be regulated by urapidil and perindopril.
文摘BACKGROUND: Hyperbaric oxygen (HBO) is used for treating glaucoma, and affirmative curative effect has been obtained. HBO can sensitively reflect the obviously heightened b wave of electroretinogram (ERG) of injured tissue. OBJECTIVE: To observe the effect of HBO treatment on retinal function of rats with acute experimental intraocular hypertension with ERG. DESIGN: Randomized controlled experiment. SETTING: Department of Ophthalmology, Third Xiangya Hospital, Central South University; Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University; Department of Anatomy, Xiangya Hospital, Central South University. MATERIALS: Eighteen adult healthy Wistar rats, of either gender, weighing from 150 to 250 g, were provided by the Animal Room of Central South University. Type YLCO. 5/I A baby hyperbaric oxygen chamber, type LMS-2A two-channel physiological recorder, type BG-1 retina exposure system, Jiangwan type Ⅰ stereotaxis instrument. METHODS: This experiment was carried out in the Central South University between March and September 2006. Eighteen healthy Wistar rats were made into models of acute experimental intraocular hypertension. Then, they were divided into two groups: model group and HBO treatment group, with 9 in each group. Following 7 days of HBO treatment, the rats in HBO treatment group were placed in Type YLCO. 5/I A baby hyperbaric oxygen chamber, which was pressurized with pure oxygen( volume fraction 0.825 ± 0.025).The treatment pressure was 0.2 MPa. The rats in HBO treatment group daily inhaled HBO for 80 minutes within 7 days; Rats in the model group were untouched. The performance of eyes was observed under the status of intraocular hypertension. ERG was recorded before, during and 7 days after modeling, meanwhile, the recovery rate of b wave from ERG was calculated. Recovery rate of b wave from ERG=(amplitude orb wave 7 days after modeling/amplitude orb wave before modeling)× 100%. MAIN OUTCOME MEASURES: ①Performance of eyes under the status of intraocular hypertension. ②Recovery rate orb wave of ERG. RESULTS: All the 18 rats were involved in the final analysis. ①Performance of eyes under the status of intmocular hypertension.: When intraocular pressure increased until b wave of ERG disappeared, two eyes of rats with corneal opacity, dilated pupils, pale iris and stiffened eyeballs were found. ②Recovery rate of b wave of ERG in the HBO treatment group was significantly higher than that in the model group [(60.04±19.33)% vs. (41.85 ± 13.20)%, t =3.298, P 〈 0,01]. CONCLUSION: HBO treatment can obviously promote the recovery of retinal function following acute intraocular hypertension.
文摘Angiotension-Ⅱ(A-Ⅱ) receptor maximal binding capacity (Bmax) and dissociation constants (Kd) of different blood vessels in rats with prehepatic portal hypertension were studied by radioligand binding analysis. The results showed that the A-Ⅱreceptor Bmax. in the thoracic aorta, superior mesenteric artery and portal vein of portal hypertensive animals (113. 7±19. 4 fmol/mg protein, 206.9 ±39. 3 fmol/mg protein and 31. 5±9. 2 fmol/mg protein respectively ) was all significantly lower than that of controls (146. 8±24. 5 fmol/mg protein, 297. 2±44. 7 fmol/mg protein and 53. 4±12.1 fmol/mg protein respectively, P<0. 01).The A-Ⅱ receptor Kd in the superior mesenteric artery was markedly increased in portal hypertensive animals (1. 03±0.11 nmol/L) compared with that in controls (0. 88±0. 08 nmol/L, P<0. 05). In the thoracic aorta and portal vein, the A-Ⅱ receptor Kd in portal hypertensive animals was slightly higher than that in controls, but no significant difference was observed between the two groups. The results suggested that the vascular hyporesponsiveness to A-Ⅱ in portal hypertension was caused partially by a reduction in number and a decrease in affinity of vascular A- Ⅱ receptors, and these changes might possibly lead to the formation of hyperdynamic circulation.
文摘Objective: To explore the mechanism of Chuanxiong in alleviating hypoxic pulmonary hypertension in rats by inhibiting pulmonary vascular remodeling. Methods: Thirty healthy and clean male SD rats weighing (180 - 220) g were randomly divided into three groups (n = 10): normoxia group (n), hypoxia group (H) and Chuanxiong group (L). Group N was fed in normoxic environment, and the other two groups were fed in hypoxic (9% 11% O2) environment for 4 weeks, 8 h/D, 6 days a week. Rats in group L were gavaged with Ligusticum chuanxiong solution diluted with normal saline at the concentration of 300 mg/kg, and rats in group H were gavaged with equal volume of normal saline. After 4 weeks, the mean pulmonary artery pressure was measured. After pulmonary perfusion, the right ventricular free wall and left ventricle plus ventricular septum were taken to measure the right ventricular hypertrophy index. The changes of pulmonary morphology and ultrastructure were observed under light microscope. Results: Compared with group n, the average pulmonary artery pressure and right ventricular hypertrophy index in the other two groups increased, and the thickening of pulmonary vascular wall was obvious under microscope (P Conclusion: Ligusticum chuanxiong can relieve pulmonary artery pressure in rats by inhibiting pulmonary vascular remodeling.