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.

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.

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.

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.

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.

Artificial cold exposure induced stroke in renovascular hypertensive rats and its association with cold-inducible RNA binding protein mRNA expression in brain tissue and blood pressure

BACKGROUND： High incidence of stroke at interchange period of autumn and winter was demonstrated by epidemiological survey, and the specific causes should be further investigated. OBJECTIVE： To investigate the influence of artificial cold exposure on the incidence of stroke in renovascular hypertensive rats （RHR）, and analyze the association with blood pressure and cold-inducible RNA binding protein （CIRP） mRNA expression in brain tissue. DESIGN： A completely randomized grouping design, a randomized control animal trial. SETTINGS： Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University; Department of Chemistry, Open laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong. MATERIALS： Male SD rats （n=460）, weighing 80 - 100 g were obtained from Guangdong Province Health Animal Unit. A modified RXZ-300A intelligent artificial climate cabinet （Ningbo Jiangnan Instrument Co. ,Ltd., China）. METHODS： The experiment were processed in the Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University and the Open Laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong from October 2004 to November 2005. Rats （n = 400） were operated to establish 2-kidney 2-clip RHR model as described previously. The sham-operated rats （n =60） served as normotensive controls. Eight weeks later, 300 of RHR were randomly selected according to their systolic blood pressure （SBP） and divided into 3 sub-groups （n =100 per group）： mild hypertensive group （SBP of 160 - 200 mm Hg）, moderate hypertensive group （SBP of 200 - 220 mm Hg） and severe hypertensive group （SBP 〉 220 mm Hg）. Each group was further divided into two groups （n =50） under ACE and non-ACE. Normal sham-operated SD rats （n =60）, SBP 〈 140 mm Hg, were randomly divided into two groups： Sham-operated control group （n =30） under ACE and non-ACE. To establish the ACE and non-ACE treatment, rats were housed individually in artificial climate cabinet, and ACE was designed as three cycles of 12-hour light of 22℃ （7 ： 00 - 19 ： 00） and 12-hour dark of 4℃（19 ： 00 - 7 ： 00）. The non-ACE group was kept at 22℃ throughout the experiment. MAIN OUTCOME MEASURES： Blood Pressure changes were measured and stroke symptom were observed; Expression of the CIRP were examined by reverse transcription-polymerase chain reaction. RESULTS： Finally 360 rats were involved in the analysis of results. ①Incidence of stroke： The incidence of stroke in 2k2c RHR was significantly higher after a three-day intermittent （12-hour） ACE （29.3%） as compared with that in non-ACE （17.3%） （P 〈 0.05）. Furthermore, the severe hypertensive 2k2c RHR （BP 〉 220 mm Hg） was found to have much higher incidence of stroke （66%, 33/50） than the mild （8%, 4/50） and moderate （18%） hypertensive 2k2c RHR. ②CIRP mRNA in brain tissue： ACE treatment stimulated the mRNA expression of CIRP in non-stroke 2k2c RHR but not in stroke 2k2c RHR （P 〈 0.05）. CONCLUSION： High blood pressure and low expression of CIRP are associated with ACE induced stroke.

The Expression of VIP and SP in the Cochlea of Spontaneously Hypertensive Rats and Its Implication

To investigate the expression of vasoactive intestinal peptide (VIP) and substance P (SP) in the cochlea of spontaneously hypertensive rat (SHR), and to assess the function of VIP and SP in the cochlea following the damage of hypertension, hearing thresholds of ABR were observed and the fixative (4% paraformaldehyde) was pumped through the circulatory system. Adult Wistar rats (3 months, n=20) served as the control group and SHRs (3 months, n=20) as the hypertension group. Bullas were taken out and cochleas were irrigated in vitro with the same fixative. The number of base turn's spiral ganglions in the sections was counted. The expression of VIP and SP were detected by SABC method and the images of the sections were analyzed. The number of base turn's spiral ganglsons in the hypertension group was significantly less than in the normal group (P<0.01). VIP and SP were expressed in the spiral ganglion cytoplasma and stria vascularis of the two groups. There were no significant difference in the expression of VIP and SP in spiral ganglion cytoplasma (P>0.05) between the two groups. However, in stria vascularis the expression of VIP in the hypertension group was higher than in the normal group (P<0.05), and no significant difference in SP was found between the two groups. It was suggested that VIP not only contributed to the regulation of the cochlea microcirculation, but also made the neurotransmitter in the pathway of the auditory system. However, SP made only the neurotransmitter in the pathway of the auditory system.

Yizhining elixation improves sustained attention deficit and impulsiveness of spontaneous hypertensive rats

BACKGROUND： The core symptoms of attention deficit, impulsiveness, hyperactivity of attention deficit hyperactivity disorders （ADHD） can concurrently present in spontaneous hypertensive rats. Neuropathological, biochemical and pharmacological studies also support it. Spontaneous hypertensive rats are one kind of best ADHD animal models, which has been accepted at present. Yizhining elixation can reinforce kidney and calm liver, strengthen spleen and nourish heart, benefit intelligence and focus attention, but its therapeutic effect on treatment of ADHD needs to be further investigated. OBJECTIVE： To observe the effect of Yizhining elixation on the persistent active attention deficit and impulsiveness of rats with spontaneous hypertension. DESIGN： Observational and controlled analysis. SETTING： Department of Pediatrics, the First Affiliated Hospital of Guangzhou University of Chinese Medicine. MATERIALS： Thirty-six male rats with spontaneous hypertension, of clean grade, were involved in this experiment. The involved rats were provided by Shanghai SLAC Laboratory Animal Co., Ltd., and they did not undergo any experiments; Yizhining elixation was composed by Guiban, Shenglonggu, Yuanzhi, Shichangpu, Yejiaoteng, Shudi, Dangshen, Yunling, Fuxiaomai, Wueizi. etc. Crude drug, provided by Outpatient Dispensary, Affiliated Hospital of Guangzhou University of Chinese Medicine, was prepared into water elixation, which contained crude drug of 1.154 g/mL. METHODS： This experiment was carried out in the Department of Pediatrics, First Affiliated Hospital of Guangzhou University of Chinese Medicine between March and July 2005. The involved rats were randomized into 3 groups： Yizhining high dose group, Yizhining low dose group and blank control group, with 12 rats in each. Changes in sustained attention and impulsiveness of rats were detected before and after administration of Yizhining elixation by ＂5-choice serial response time task＂ method. Following above-mentioned training and detection, rats in each group were daily drenched with Yizhining elixation once for 14 days successively. Rats in the Yizhining High-dose and low-dose groups we, e drenched with 12.6 mL/kg and 6.3 mL/kg Yizhining elixation （diluted to 25 mL/kg） respectively, and those in the blank control group were drenched with 12.5 mL/kg normal saline. On the 14^th day after administration, the ratios of correct and immature response of rats were re-detected for 3 days successively by formal detection method for later analysis. The sustained attention of rats was evaluated with ratio of correct response： Ratio of correct response=[times of correct response/（times of correct response ＋ times of incorrect response）]; impulsiveness was evaluated with the ratio of immature response： ratio of immature response=[times of immature response/ （times of correct response＋times of incorrect response＋times of omission＋times of immature response） ]. MAIN OUTCOME MEASURES： The effects of different doses of Yizhining elixation on the sustained attention （ratio of correct response） and impulsiveness （ratio of immature response） of spontaneous hypertensive rats. RESULTS： Thirty-six spontaneous hypertensive rats were involved in the final analysis. The ratio of correct response of rats in the Yizhining high dose and low dose groups after administration was （98.9±2.30）% and （96.6±4.00） %, respectively, which was significantly higher than that before administration [ （80.4±11.5 ） %, （839±8.90） %, P 〈 0.01] and that in the blank control group[ （83.3±6.30） %, P 〈 0.01]. The ratio of immature response of rats in the Yizhining high dose and low dose groups after adminisWafion was （5.04 ±1.04 ） %, （7.23 ± 1.22 ） %, respectively, which was lower than that before administration [ （9.85 ±2.50） %, （9.40±1.73 ） %, P 〈 0.05] and that in the blank control group [ （ 9.42 ±1.64） %, P 〈 0.01 ]. CONCLUSION： Yizhining elixation can improve the sustained attention and impulsiveness of spontaneous hypertensive rats.

Effect of Xinjikang on left ventricular hypertrophy remodeling in hypertensive rats

Objective:To investigate the effects of Xinjikang on the left ventricular hypertrophy remodeling and myocardial activity in hypertension.Methods:Sixty Wistar rats were randomly divided into four groups.The pressure-loaded left ventricular hypertrophy model was established with abdominal aorta ligation method.Rats in A and B groups were intragastrically administered with physiological saline,while C and D groups were administered with Xinjikang and metoprolol,respectively.The changes in blood pressure.E/A ratio,myocardial pathological morphology,myocardial lipoperoxides and superoxide dismustase activity in four groups were observed and compared before and after treatment.Results:There were statistically significant differences in E/A ratio between C group after treatment and model group(P<0.05).while no difference was observed between A and D groups(P>0.05);after treatment the myocardial lipoperoxides and superoxide dismustase contents in C and D groups were improved significantly compared with model group(P<0.05).Conclusions:Xinjikang can improve myocardial injury,restore myocardial parenchyma and myocardial interstitial remodeling functions in hypertensive rats with the left ventricular hypertrophy.

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.

Sesamin enhances nitric oxide bioactivity in aortas of spontaneously hypertensive rats

OBJECTIVE To explore the underlying mechanisms involved in the effect of sesamin on aortic NO bioactivity in spontaneously hypertensive rat(SHR).METHODS Sesamin was orally administered for consecutive 8 weeks in SHR.Systolic blood pressure(SBP)was measured using the tail-cuff method.The aortas were isolated and in vitro vascular reactivity studies were performed.Superoxide anion production in carotid arteries was assessed by dihydroethidium fluorescence staining.The protein expression of endothelial nitric oxide synthase(eNOS),phosphorylated eNOS(P-eNOS),dihydrofolate reductase(DHFR),nicotinamide adenine dinucleotide phosphate(NADPH)oxidase subunit p47 phox and copper,zinc-superoxide dismutase(Cu/Zn-SOD)in aortas was detected by Western blotting.The dimeric form of eNOS in aortas was determined by low-temperature SDS-PAGE.Aortic level of nitrotyrosine and activities of antioxidant enzymes,namely,total SOD(T-SOD),glutathione peroxidase(GPx)and catalase were also detected.RESULTS In SHR,sesamin treatment reduced SBP,improved vascular relaxation induced by acetylcholine and enhanced aortic NO bioactivity.Sesamin treatment enhanced NO biosynthesis in SHR aortas was due to upregulated P-eNOS and suppressed eNOS uncoupling,and the latter effect might be attributed to decreased nitrotyrosine and upregulated DHFR.Sesamin also reducd the NO oxidative inactivation and decreased the superoxide anion production through downregulation of p47 phox and amelioration of eNOS uncoupling.In addition,sesamin treatment did not alter the levels of GPx and catalase activity but obviously reduced the compensatory elevated T-SOD activity and Cu/Zn-SOD protein expression.CONCLUSION Chronic treatment with sesamin could reduce hypertension and improve endothelial dysfunction through enhancement of NO bioactivity in SHRs aortas.

Taurine supplementation in spontaneously hypertensive rats: Advantages and limitations for human applications

Taurine(2-aminoethanesulfonic acid) is a β-amino acid found in many tissues particularly brain, myocardium, and kidney. It plays several physiological roles including cardiac contraction, antioxidation, and blunting of hypertension. Though several lines of evidence indicate that dietary taurine can reduce hypertension in humans and in animal models, evidence that taurine supplementation reduces hypertension in humans has not been conclusive. One reason for the inconclusive nature of past studies may be that taurine having both positive and negative effects on cardiovascular system depending on when it is assessed, some effects may occur early, while others only appear later. Further, other consideration may play a role, e.g., taurine supplementation improves hypertension in spontaneously hypertensive rats on a low salt diet but fails to attenuate hypertension on a high salt diet. In humans, some epidemiologic studies indicate that people with high taurine and low salt diets display lower arterial pressure than those with low taurine and high salt diets. Differences in techniques for measuring arterial pressure, duration of treatment, and animal models likely affect the response in different studies. This review considers both the positive and negative effects of taurine on blood pressure in animal models and their applications for human interventions.

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.

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.

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).

AngiotensinⅡor epinephrine hemodynamic and metabolic responses in the liver of L-NAME induced hypertension and spontaneous hypertensive rats

AIM To study hepatic vasoconstriction and glucose release induced by angiotensin(Ang)Ⅱ or Epi in rats with pharmacological hypertension and spontaneously hypertensive rat(SHR).METHODS Isolated liver perfusion was performed following portal vein and vena cava cannulation; AngⅡ or epinephrine(Epi) was injected in bolus and portal pressure monitored; glucose release was measured in perfusate aliquots. RESULTS The portal hypertensive response(PHR) and the glucose release induced by AngⅡ of L-NAME were similar to normal rats(WIS). On the other hand, the PHR inducedby Epi in L-NAME was higher whereas the glucose release was lower compared to WIS. Despite the similar glycogen content, glucose release induced by AngⅡ was lower in SHR compared to Wistar-Kyoto rats although both PHR and glucose release induced by Epi in were similar. CONCLUSION AngⅡ and Epi responses are altered in different ways in these hypertension models. Our results suggest that inhibition of NO production seems to be involved in the hepatic effects induced by Epi but not by AngⅡ; the diminished glucose release induced by AngⅡ in SHR is not related to glycogen content.

Cardiac Myeloperoxidase Activity Is Elevated in Hypertensive Pregnant Rats

Myeloperoxidase（MPO） is released from activated neutrophils. The inflammation in preeclampsia was found to be associated with endothelial dysfunction. We hypothesized that cardiac and circulating MPO levels are elevated in hypertensive pregnancy. Systolic and diastolic blood pressure and heart rate were measured on pregnancy days 14, 16, 18 and 20 in normal pregnant and hypertensive pregnant rats. Left and right ventricle weights, the number of viable fetuses, litter size, fetal and placenta weights were recorded on gestational day 21. Circulating and cardiac MPO activities, soluble fms-like tyrosine kinase-1（sFlt-1） and vascular endothelial growth factor（VEGF） and nitric oxide（NO） were detected. The results showed increases in cardiac（left, but not right ventricle） and circulating MPO activities, and concomitantly lower number of viable fetuses, litter size, and fetal and placenta weights, and decreases in NO in hypertensive pregnant rats. Also, the increases in circulating sFlt-1 and VEGF were found in hypertensive pregnant group. In conclusion, maternal and fetal detrimental changes along with increases in circulating sFlt-1 and VEGF in hypertensive pregnancy may be associated with increases in cardiac and circulating MPO activities, confirming the causative role of inflammatory response in preeclampsia.

Antioxidant role of heme oxygenase-1 in prehepatic portal hypertensive rats

瞄准：在氧化的肝地位和这项活动和表示上学习胆红素的效果他我在老鼠肝损伤的 oxygenase-1 (HO-1 ) 由 prehepatic 门静脉高血压导致了。方法：Wistar 雄的老鼠，称 200-250 g，在随机被划分成二个组：有调整 prehepatic 门静脉结扎(PPVL ) 导致的 prehepatic 门静脉高血压(PH ) 的一个组和另外的组对应于假冒的操作老鼠。门压力，氧化压力参数，抗氧化剂酶， HO-1 活动和表示和肝的正弦曲线血管舒张被测量。结果：在 PPVL 老鼠，氧化应力被在减少的谷胱甘肽(GSH ) 的反应物质(TBARS ) 内容和减少铺平的 thiobarbituric 酸的显著增加证实。当 HO-1 的活动和表示被提高时，肝抗氧化剂酶，超级氧化物歧化酶(草皮) ，过氧化氢酶(猫) 和谷胱甘肽过氧化物酶(GSH-Px ) 的活动也被减少。胆红素(5 mumol/kg 体重) 的管理在实验的结束前的 24 h 完全阻止了所有这些效果。有 Sn-protoporphyrin IX (Sn-PPIX ) 的预告的处理(100 mug/kg 体重， i.p ) ，一个有势力禁止者惊讶，完全废除了氧化压力并且每氧化象类脂化合物的增加一样在肝 GSH 层次挑起了细微减少。而且，一氧化碳，另一他我分解代谢的产品，在在 PPVL 的肝的区域组织的正弦曲线导致了重要增加。有 Sn-PPIX 的 PPVL 老鼠的预告的处理完全阻止了这效果。结论：这些结果在 prehepatic 门 hypertensive 老鼠在表示上建议 HO-1 的一个有益的角色。

Effect of 2-Selenium Bridged β-Cyclodextrin,Glutathione Peroxidase Mimic on Stroke of Stroke-prone Spontaneously Hypertensive Rats

To investigate the treatment effect of 2-selenium bridged β -cyclodextrin(2-SeCD),a GPX mimic,on the stroke of stroke-prone spontaneously hypertensive rats(SHRSP),fifty-two SHRSP of 8-week old were randomly divided into four groups A,B,C and control group D. The rats of groups A,B,C and D were given 1.0%-1.5% NaCl mass fraction as drinking fluid. After onset of stroke,groups A,B and C were given \{orally\} 16.05,160.5 and 1605 mg·kg -1 ·day -1 of 2-SeCD,respectively,and group D was given water for \{2 weeks.\} The clinical score of stroke,systolic blood pressure(SBP),survival time of rats were recorded and the histopathologic examinations of their brain and carotid artery were made after decapitation. The clinical scores of stroke after treatment with 160.5 mg·kg -1 ·day -1 (Group B) and 1605 mg·kg -1 ·day -1 (Group C) of 2-SeCD are 2.55±0.98 and 1.98±0.79,respectively,those are obviously lower than that of group D(3.41±0.83,p<0.01). The survival days in group B(10.0±8.6) and group C(14.4±7.9) are longer than that for group D(4.7±2.9,p<0.01). The electron microscope study showed that the endothelium of carotid artery was near to normal in group B and group C,while it was seriously injured in control group D and mildly injured in group A. 2-SeCD may effectively be used to treat the stroke for SHRSP.