Underlying anti-hypertensive mechanism of the Mizuhopecten yessoensis derived peptide NCW in spontaneously hypertensive rats via widely targeted kidney metabolomics

The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.

Epigallocatechin-3-gallate exerts antihypertensive effects and improves endothelial function in spontaneously hypertensive rats

Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days.Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment.The vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also measured.Moreover,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was determined.Results:The systolic blood pressure was significantly decreased in SHR treated with EGCG.The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group.EGCG also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in SHR.Conclusions:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)receptors.An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.

Effects of hot-water extract of <i>Paecilomyces hepiali</i>on hypertension parameters in Spontaneously Hypertensive Rats

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.

Protective Effects of Nobiletin on Hypertension and Cerebral Thrombosis in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP)

Some citrus flavonoids have been reported to possess antioxidant activities that moderate endothelial dysfunction and show protective effects on cardiovascular disease. We have investigated the protective effects of nobiletin (5,6,7,8,3’,4’-hexamethoxy flavone) derived from the peel of Citrus depressa Hayata (Shiikuwasha), a citrus fruit produced in Okinawa prefecture in Japan on hypertension and thrombogenicity in cerebral vessels of stroke-prone spontaneously hypertensive rats (SHRSP). Nobiletin was added to the diet of male SHRSP (7 weeks old) for 4 weeks. The age-related increase in systolic blood pressure usually observed in SHRSP was significantly suppressed in the treated animals. Thrombogenesis in pial blood vessels, determined using a He-Ne laser technique, and antioxidant activity, assessed by measuring urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG), were significantly reduced after treatment. Urinary nitric oxide (NO) metabolites and acetylcholine-induced endothelial relaxation were increased after dietary intervention. These results strongly suggested that antihypertensive and antithrombotic effects of nobiletin may be related to an increase in bioavailable NO, possibly mediated by the scavenging of reactive oxygen species (ROS).

Effect of Salvia Miltiorrhiza Injection on Blood Pressure and Cardiac Function in Rats with Gestational Hypertension and Preeclampsia

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.

Effects of Total Flavonoids ofHippophae RhamnoidesL.on Intracellular Free Calciumin Cultured Vascular Smooth Muscle Cells of Spontaneously Hypertensive Rats and Wistar-Kyoto Rats

To explore the effects of total flavonoids of Hippophae rhamnoides L. （TFH） quercetin （Que） and isorhamnetin （Isor） on the intracellular free calcium （[Ca^2＋]） in vascular smooth muscle cells （VSMC） of spontaneously hypertensive rats （SHR） and Wistar-Kyoto rats （WKY）. Metheds： Fluo 3-acetoxymethylester（Fluo-3/AM） was used to observe the effects of TFH （100mg/L） and its essential monomers, namely Que （10^-4mol/L） and Isor （10^-4mol/L） on changes of [Ca^2＋]1 in cultured SHR and WKY VSMC （abbr. to Ca-SHR ＆ Ca-WKY） following exposure to high K^＋, norepinephrine （NE） and angiotensin Ⅱ （AngⅡ）, and to compare with the effects of verapamil （Ver）. Results： （1） TFH, Que and Isor had inhibitory effects on resting Ca-SHR （P〈0.05）, but had no significant effects on Ca-WKY （P〉0.05）. （2） High K^＋ could increase Ca-SHR more significantly than Ca-WKY （P〈0.05）; TFH, Que and Isor could inhibit the elevation of [Ca^2＋]1 induced by high K^＋ -depolarization, with the effects similar to that of Ver, and the effect on Ca-SHR was more significant than that on Ca-WKY （P〈0.05）. （3） NE and Ang Ⅱ could increase Ca-SHR more significantly than Ca-WKY （P〈0.05）, TFH, Que and Isor had remarkably inhibitory effect on the elevation of Ca-SHR and Ca-WKY induced by NE or Ang Ⅱ. （4） In the absence of extracellular Ca^2＋ , TFH, Que and Isor also had certain inhibitory effect on Ca-SHR and Ca-WKY induced by NE, and the effect on the former was more significant than that on the latter（P〈0.05）. Ceaclusiea： TFH, Que and Isor might decrease the levels of [Ca^2＋], in VSMCs by blocking both voltage-dependent calcium channels （VDC） and receptoroperated calcium channels （ROC） in physiological or pathological state, which may be one of the important mechanisms of their hypotensive and protective effects on target organs in patients with hypertension.

Effect of Salvia Miltiorrhiza Bge on Left Ventricular Hypertrophy and the Expression of Tumor Necrosis Factor-α in Spontaneously Hypertensive Rats

The effects of salvia miltiorrhiza Bge (SMB) on left ventricular hypertrophy (LVH) and the expression of tumor necrosis factor-α (TNF-α) in the left ventricle of spontaneously hypertensive rats and the action mechanism were investigated. Normal Wistar-kyoto (WKY) rats were used as negative control, and spontaneously hypertensive rats (SHR) were randomly assigned to receive pla- cebo or SMB. SMB (1 g/kg·d) was injected intraperitoneally for 12 weeks. Systolic blood pressure (SBP) and left ventricular mass index (LVMI) were measured. HE, VG and immunohistochemical staining combined with computed morphometry were employed to evaluate the cardiomyocyte size, diameter, the collagen volume fraction (CVF), perivascular circumferential area (PVCA), and tumor necrosis factor-α (TNF-α) expression in the left ventricular tissue. The results showed, as compared with WKY rats, the SBP, LVMI, cardiomyocyte size, diameter, CVF, PCVA, and TNF-α expression were increased markedly in the 20-week-old spontaneously hypertensive rats. SMB decreased LVMI (P<0.01), size of cardiomyocytes (P<0.01), collagen volume fraction (P<0.01), perivascular circum- ferential area (P<0.01), and TNF-α expression (P<0.01), but had no effect on SBP (P>0.05). It was suggested that chronic administration of SMB could inhibit and reverse the development of LVH in spontaneously hypertensive rats independent of BP. TNF-α may be involved in the reversal mecha- nism of LVH by SMB.

Effect of Salvia Miltiorrhiza on Left Ventricular Hypertrophy and Cardiac Aldosterone in Spontaneously Hypertensive Rats

Chronic treatment with Salvia Miltiorrhiza preventing left ventricular hypertrophy (L VH) and its possible mechanism- inhibiting the action of cardiac aldosterone in spontaneously hypertensive rats (SHR) were investigated.Normotensive Wistar- kyoto (WKY ) rats and SHRs were used.Part of SHRs was treated with Salvia Miltiorrhiza for 12 weeks.Systolic blood pres- sure (SBP) and left ventricular mass index were measured.Sections of heart tissue were stained with HE method and Van Gieson method.Collagen volume fraction was determined in the leftven- tricle by automatically quantitative m orphometry.Cardiac aldosterone concentration was measured by radioimm unoassay.The results indicated thatcom pared with WKY rats,SHRs exhibited high- er SBP,left ventricular collagen volume fraction,and aldosterone concentration (all P<0 .0 5 ) . After the treatm ent with Salvia Miltiorrhiza,SBP,left ventricular collagen volum e fraction,and aldosterone concentration in SHR were decreased as compared with control group (P<0 .0 5 ) ex- cept SBP.It was concluded thatchronic treatment with Salvia Miltiorrhiza could preventleftven- tricular hypertrophy in SHR,significantly inhibit collagen compositions in left ventricle.The m echanism was probably related with the inhibition of the cardiac aldosterone action.

Telmisartan Attenuates the Growth of Epithelium-like Cells and Glomerular Injury in Spontaneously Hypertensive Rats

The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis in hypertensive nephropathy are not fully understood.In the present study,we investigated the correlation of epithelium-like cells with glomerular injury,and the effects of early drug intervention with telmisartan,an anti-hypertensive drug,on the growth of epithelium-like cells.The results showed that the epithelium-like cells were obviously observed lining along the luminal surface of Bowman’s capsule in glomeruli,significantly resulting in the atrophy of the glomerular tuft.Some of the epithelium-like cells strongly expressed proliferating cell nuclear antigen(PCNA)and vimentin,indicating active cellular proliferation.The incidence of epithelium-like cells varied from 13.6%to 54.4%of glomeruli in 48-week-old SHRs,and from 5.1%to 18.0%of glomeruli in age-matched Wistar-Kyoto(WKY)rats(P<0.01).The linear regression analysis further confirmed an obvious correlation between the incidence of epithelium-like cells and the glomerular injury.Moreover,early intervention with telmisartan could dramatically attenuate the progression of epithelium-like cells growth.However,no significant effect of telmisartan on the established epithelium-like cells was observed.Taken together,we demonstrated the involvement of abnormal epithelium-like cells growth in glomerular injury during hypertensive nephropathy in SHRs,and firstly showed the positive effects of the anti-hypertensive drug on the progression of epithelium-like cells growth.

Neuropathy optic glaucomatosa induced by systemic hypertension through activation endothelin-1 signaling pathway in central retinal artery in rats

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.

Continuous Subcutaneous Administration of Miso Extracts Attenuates Salt-Induced Hypertension in Dahl Salt-Sensitive Rats

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.

The effects and mechanisms of total flavonoids of Cydonia oblonga Mill. on myocardial hypertrophy in spontaneously hypertensive rats

Aim To study the activity and mechanism of inhibition of myocardial hypertrophy of total flavonoids of Cydonia oblonga Mill. in spontaneously hypertensive rats. Methods Total flavonoids of COM （COMF） were sepa- rated and purified by the optimal process. SHtl were divided into 6 groups： SHR control group （SHR） , captopril group （SHR ＋ CAP, 25 μg · g^-1）, Eucommia ulmoides Oliver group （SHR ＋ EUO, 30 μg · g^-1）, low （SHR ＋ COMF-L, 40 μg · g^-1） ,middle （SHR ＋ COMF-M, 80 μg· g^-1） and high dose （SHR ＋ COMF-H, 160 μg · g^-1） of COMF groups. Wistar-Kyoto （WKY） rats （n= 8 ） were given distilled water as control The drugs were given by intragastric administration for 16 weeks. The histological and pathological examination of the heart were performed and organic damage were valued. The levels of Ang II and ALD in blood and heart were evaluated. The mRNA and protein expression of ACE, ACE2 and AT~ was determined by RT-PCR and Western blot to evaluate the effect of COMF on RAAS. Results Compared with SHR control group, HW, HW/BW, LVM and LVM/BW de- creased in SHR ＋ COMF-M and SHR ＋ COMF-H groups; Cadiomyocyte hypertrophy was inhibited in COMF groups; The concentration of Ang 11 and ALD in heart and blood decreased; ACE and AT1 mRNA and protein ex- pression in heart tissue decreased while ACE2 mRNA expression increased （P 〈 0.01 or P 〈 0.05） , Conclusion Total flavonoids of Cydonia oblonga Mill. showed the effect of inhibition of myocardial hypertrophy in spontaneously hypertensive rats and the mechanism was related to. inhibit the activity of Renin-angiotensin-aldosterone system.

Chemical renal artery denervation with appropriate phenol in spontaneously hypertensive rats

Objective To explore the effectiveness of renal denervation (RDN) on blood pressure with the appropriate dosage of phenol/ethanol solution in spontaneously hypertensive rats (SHRs). Methods RDN was performed on the bilateral renal artery. Forty SHRs were divided into four groups according on the dosage of phenol (10% phenol in absolute ethanol): sham group, 0.5 mL phenol group, 1 mL phenol group and 1.5 mL phenol group (n = 10 in each group). Blood pressure was measured by tail-cuff plethysmography. Plasma creatinine was determined four weeks after the treatment. The kidneys and renal arteries were collected and processed for histological examination. Results A sustained decrease in systolic blood pressure (SBP) was only observed after the application of 1 mL phenol for four weeks, while SBP was lowered during the first week after RDN and increased in the following three weeks in the 0.5 mL and 1.5 mL phenol groups compared with the sham group. Renal norepinephrine (NE) was significantly decreased four weeks after RDN in the 1 mL and 1.5 mL phenol group compared with the sham group, but not in the 0.5 ml group. RDN with 1 mL phenol obviously reduced glomerular fibrosis. Histopathological analysis showed that tyrosine hydroxylase immunoreactivity was lower in the 1 mL and 1.5 mL phenol groups compared with the sham group. Moderate renal artery damage occurred in the 1.5 mL phenol group. Conclusion Chemical denervation with 1 ml phenol (10% phenol in absolute ethanol) effectively and safely damaged peripheral renal sympathetic nerves and contributed to the sustained reduction of blood pressure in SHRs.

Protective effect of sodium ferulate on cardiac hypertrophy in spontaneously hypertensive rats

OBJECTIVE To investigate the inhibitory effect and mechanism of sodium ferulate(SF)on myocardial hypertrophy in spontaneously hypertensive(SHR).METHODS Forty 14-week-old SHR male rats were randomly divided into model group(SHR,receive distilled water)and SF treatment groups(SF 20,40 and 80 mg·kg^-1 per day,respectively).Age-matched male Wistar-Kyoto(WKY)rats gavaged with distilled water served as controls.After 12 weeks of treatment,the effects of SF on cardiac hypertrophy were evaluated using echocardiographic measurement,pathological analysis and the expression of atrial natriuretic peptide(ANP),myosin heavy chainβ(β-MHC)-a gene related to myocardial hypertrophy.In order to explore the mechanism of SF on myocardial hypertrophy,the calcium-sensing receptor(CaSR),calcineurin(CaN),nuclear factor of activated T cell 3(NFAT3),phosphorylation NFAT3(p-NFAT3),zinc finger transcription factor(GATA4),phosphorylation GATA4(p-GATA4),protein kinase Cβ(PKC-β),Raf-1,extracellular regulated protein kinase 1/2(ERK 1/2),phosphorylation ERK1/2(p-ERK 1/2)and mitogen-activated protein kinase phosphatase-1(MKP-1)were detected.RESULTS The myocardial hypertrophy parameters,myocardial cell cross section area,left ventricular wall thickness and expression of ANP and β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 were significantly increased,while the left ventricular cavity was significantly smaller,expression of p-NFAT3 and MKP-1 were significantly decreased,meanwhile,the ultra⁃structure of cardiomyocytes was significantly damaged in 26-week-old SHR rats.Notably,SF significantly ameliorated myocardial hyper⁃trophy in 26-week-old SHR rats;suppressed the overexpression of ANP,β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 and increased the expression of p-NFAT3 and MKP-1.CONCLUSION SF can inhibit cardiac hypertrophy in SHR rats,and the mechanism may be related to the inhibition of CaSR mediated signaling pathway.

Changes in activity of superoxide dismutase and content of malondialdehyde in rats with monocrotaline-induced pulmonary hypertension

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.

A hippocampal anti-hypertensive mechanism induced by twirling reinforcing-reducing manipulation in rats

Objective:To investigate a hippocampal anti-hypertensive mechanism induced by twirling reinforcingreducing manipulation(TRRM)using proteomics in rats.Methods:Forty-two male spontaneously hypertensive rats were randomly divided into 3 groups,and 14 Wistar-Kyoto rats were served as control group.In the twirling reinforcing(TRF)group,needles were directly inserted into the Taichong(LR 3)point,then thumbs were moved heavily forward and lightly backward for 3 min,while needles remained inserted for 17 min.In the twirling reduction(TRD)group,the same treatment was applied as in the TRF group except that the thumb moved lightly forward and heavily backward.In the model and control groups,only the corresponding grasping and fixation were applied.All interventions were conducted for 14 days.The blood pressure(BP)of all rats was measured one day before intervention and every other day after.Then hematoxylin-eosin(H&E)staining,label-free and parallel reaction monitoring proteomic techniques were used to assess hippocampal samples from each group.Results:Systolic BPs showed a significant decrease in the TRF and TRD groups compared with the model group(P<.01).In the model group,H&E staining showed obvious pathological changes in the hippocampus,while in the TRF and TRD groups,the hippocampal morphology was only slightly altered.Labelfree proteomic analysis revealed 1163 differential protein expressions between groups.Gene Ontology enrichment analysis confirmed that the differentially expressed proteins were enriched in different biological processes,cellular components,and molecular functions.Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that TRRM proteins were expressed in the serotonergic synapse pathway,renin-angiotensin system,the mitogen-activated protein kinase signaling pathway,and the peroxisome pathway,which were all also related to BP regulation.Conclusion:TRRM can significantly lower the BP of SHRs.The mode of action may be through the activation of various protein pathways in the hippocampus that are related to BP regulation.

The effect of bone marrow mesenchymal stem cell transplantation on hypoxic pulmonary hypertension in rats

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.

Antihypertensive Properties on Spontaneously Hypertensive Rats of Peptide Hydrolysates from Silkworm Pupae Protein

Peptide hydrolysates of silkworm pupae protein with molecular weight of less than 5000 Da were prepared by ultrafiltration. The extracted peptide hydrolysates of silkworm pupae protein had inhibitory action on angiotensin-I-converting enzyme activity in vitro. The hydrolysates were orally administered to spontaneously hypertensive rats (SHR) in one period and long-term (four weeks). The results showed that the systolic blood pressure (SBP) of the treatment groups decreased in a dose-related manner. After one oral administration of silkworm protein hydrolysates with doses of 60, 20 and 5 mg/kg, the SBP of SHR decreased by 21.5, 13.8, and 9.0 mmHg in 1.5 h. After four weeks of the treatment in 80 mg/kg, the SBP decreased by 25 mmHg, with the antihypertensive activity close to 4 mg/kg of captopril;the SBP of the 40 mg/kg dose group also decreased by 17.5 mmHg. The peptide hydrolysate did not affect the SBP in normal, non-hypertensive rats in one period and long-term treatments. The acute toxicity research showed that the peptide hydrolysates were safe and without side effects. This research would be helpful in exploring the silkworm protein peptides as functional components for the antihypertension treatment.

Effect of Hypertension on Hearing Function,LDH and ChE of the Cochlea in Older Rats

The relationship between the hypertension and the aging process of hearing organ was investigated Twenty Wistar 3-month old rats and 20 Wistar 12-month old rats, 20 spontaneously hypertensive rat stroke-prone (SHRSP) 3-month old rats and 20 SHRSP 12-month old rats free of middle ear infections as observed under otomicroscopy, with normal tympanic membrane and auricle reflex, were selected to be divided into two experimental groups and two control groups respectively The tail artery blood pressure was measured non-invasively The threshold of auditory brainstem response (ABR) was measured by Spirit TM evoked potential meter The LDH and ChE staining in the inner ear was performed and the optical density was analyzed by the HPIAS analysis system The results showed that there was no difference in the ABR thresholds, the activities of LDH and ChE between Wistar 3-month old group and SHRSP 3-month old group ( P >0 05) The mean value of ABR threshold and the activities of LDH and ChE in the Wistar 12-month old group at relevant sections were significantly greater than those in the two 3-month old groups ( P< 0 05), whereas the mean value of ABR threshold and the activities of LDH and ChE in the SHRSP 12-month old group at relevant sections were significantly higher than those in the 3-month old control group ( P< 0 01) It was concluded that presbycusis existed in the Wistar 12-month old group rats The glycogenosis and the abnormal secretion of neural transmitter were discerned after hypertension All the above factors may worsen the aging of the hearing system