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.S...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.展开更多
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- rate...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.展开更多
Aim To study the anti-hypertensive effect of total flavonoids of Cydonia oblonga Mill. in spontaneously hypertensive rats, then preliminarily investigate the mechanism of action based on anti-inflammatory function. Me...Aim To study the anti-hypertensive effect of total flavonoids of Cydonia oblonga Mill. in spontaneously hypertensive rats, then preliminarily investigate the mechanism of action based on anti-inflammatory function. Methods Total flavonoids of COM （COMF） were separated and purified by the optimal process, SHR were divid- ed into 6 groups as SHR control group （SHR）, captopril group （CAP, 25mg· kg^-1 · d^-1）, Eucommia ulmoides Oliver group （EUO, 30 mg · kg^-1· d^-1）, low （COMF-L, 40 mg · kg^-1· d^-1）, middle （COMF-M, 80 mg · kg^-1 · d^-1） and high dose （COMF-H, 160 mg · kg^-1· d ^-1） of COMF groups. 8 Wistar-Kyoto （WKY） rats were given distilled water instead as control. The drugs were given by intragastric administration for 16 weeks, then the levels of IL-1β, IL-6, IL-10, TNF-α and CRP in serum were tested. Results Compared with WKY group, the levels of IL-I~, IL-6, TNF-α and CRP were increased and IL-10 was decreased; Compared with SHR group, the levels of IL-1β, IL-6, TNF-α and CRP were decreased in COMF groups （P 〈0.01 or P 〈0.05） , while IL-10 was increased a little but without any significant difference （P 〈 0.05 ）. Conclusion Total flavonoids of Cydonia ob- longa Mill. showed the anti-hypertensive activity in spontaneously hypertensive rats and the mechanism was related to the function of anti-inflammatory.展开更多
Objective Telomere length, as an emerging marker of biological age,isrelatedwithhypertension.Ouraimistoinvestigatethe relationship between telomere trajectory and blood pressure change as well as the incident cardiova...Objective Telomere length, as an emerging marker of biological age,isrelatedwithhypertension.Ouraimistoinvestigatethe relationship between telomere trajectory and blood pressure change as well as the incident cardiovascular events in a longitudinal hypertensive cohort in China.展开更多
Objective To investigate the effects of simvastatin compared with standard treatment on cardiovascular outcomes and all-cause mortality in high-risk hypertensive patients with a high–normal level of total cholesterol...Objective To investigate the effects of simvastatin compared with standard treatment on cardiovascular outcomes and all-cause mortality in high-risk hypertensive patients with a high–normal level of total cholesterol(TC).Methods In a randomized,open-label,blinded-endpoint trial,hypertensive patients at high risk for cardiovascular events from 180 clinical centers in China were assigned to receive treatment with amlodipine plus amiloride/hydrochlorothiazide(n=6,776)or telmisartan(n=6,766).展开更多
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 ...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.展开更多
Objective Recent evidence has indicated that hypertension is associated with impaired cognitive function. However, the prevention of cognitive disorders with antihypertensive therapy remains controversial.The trial pr...Objective Recent evidence has indicated that hypertension is associated with impaired cognitive function. However, the prevention of cognitive disorders with antihypertensive therapy remains controversial.The trial provided evidence to compare the efficacy on cognitive function with the combination of amlodipine with diuretics or angiotensin II receptor blocker.展开更多
OBJECTIVE Nowadays,with the living habits and diet structure changes,the morbidity and mortality of hypertension has been rising yearly,which induced by adverse lifestyles,excessive alcohol and poor diet.However,the a...OBJECTIVE Nowadays,with the living habits and diet structure changes,the morbidity and mortality of hypertension has been rising yearly,which induced by adverse lifestyles,excessive alcohol and poor diet.However,the animal models of hypertension resulted from adverse lifestyles have rarely been reported.It is essential to set up some more systematic models to study the characters of hypertension and evaluate the efficacy of traditional Chinese medicine(TCM).METHODS To build the rat model of human lifehabitual hypertension,SD rats had free access to alcohol with high-sucrose-fat diet(AHSFD),alcohol with high-fat diet(AHFD),high-sucrose-fat diet(HSFD),high-fat diet(HFD)and alcohol etc.Various of indicators were detected systematically to explore the features of hypertension models which included blood pressure(BP),liver and kidney functions,the lipid profiles and indexes quantifying TCM symptoms.Then we choose one of the stable and sustained animal models,studying the effects of RPA.E(which extracted from a TCM)on modulating the level of hypertension and the preliminary mechanism in this abstract.RESULTS ①The BP level,serum TC,TG,LDL-C of AHSFD-induced and AHFD-induced rats increased significantly,while the HDL-C reduced in the 4th week.② The BP level HSFD-induced rats increased significantly in the 6th week,serum TC,TG increased in 10 th week.③ The BP level of alcohol-induced rats increased significantly in the 9th week,serum TC,TG increased in 24 th week.④ The level of serum ALT,AST,UA and Cr of all model rats increased significantly after 12 weeks.Meanwhile the microcirculation increased significantly after8 weeks.⑤ After 4-week administration,RPA.E could significantly reduce BP of AHFD-induced hypertensive rats,and could reduce the serum TC,LDL-C,HDL-C,ALT,AST level after 8-week.CONCLUSION The rats induced by AHSFD,AHFD,HSFD and alcohol can raise BP obviously with underlying hepatic and kidney damage,the lipid profiles disorder and TCM symptoms change,while the AH(S)FD-induced hypertension models are earlier and more stable.RPA.E could mildly reduce BP level,and improve the lipid profiles disorders,hepatic damage,which reflects the characteristics of TCM on antihypertensive effects.The above models have their own characteristics,can be used to study the causes and pathogenesis of hypertension complicating metabolic disorder and the related treatment drug screening.展开更多
OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,...OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,GSY,metoprolol or GSY combined with metoprolol for 4weeks.Blood pressure,which included SBP,DBP and MBP was measured by a noninvasive method every week.At the end of4 weeks,blood was drawn from the ophthalmic venous plexus to determine blood fat levels(serum TC,TG,LDL-c,HDL-c),liver function(serum ALT,AST),and kidney function(serum BUN,UA and Cr)by the ACCUTE(TBA-40FR)automatic.② The aortae of normal SD rats were prepared and cleaned from periadventitial fat and surrounding connective tissue and cut transversely into 4-mm width rings.To observe different concentration of GYS,metoprolol or GSY combined with metoprolol causing relaxation of the isolated aortic rings precontracted until a stable plateau by noradrenaline(NA)directly or in the presence of eNOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin(INDO)respectively.③ The concentrations of plasma GSY was determined by the HPLC after rats administered orally with GSY or GSY combined with metoprolol for single-dose.DAS data processing software calculated the pharmacokinetic parameters of GSY.RESULTS There was a significant synergism between GYS and metoprolol in lowering blood pressure and the concentrations of serum TC and LDL-c of SHR.The relaxant effect of GYS combined with metoprolol on the aortic rings precontracted by NA could be attenuated by L-NAME or INDO.The AUC0-tof GSY significantly increased after in conjunction with metoprolol.CONCLUSION GYS combined with metoprolol increases the concentrations of plasma GSY and synergistically lowers blood pressure based on endothelium-dependent vasodilatation function(EDVF).展开更多
OBJECTIVE To investigate the effect of hydrogen-rich saline on platelet activation in hypertensive rats.METHODS The male Wistar rats were divided into control group,hypertension group,control+hydrogen-rich saline grou...OBJECTIVE To investigate the effect of hydrogen-rich saline on platelet activation in hypertensive rats.METHODS The male Wistar rats were divided into control group,hypertension group,control+hydrogen-rich saline group and hypertension+hydrogen-rich saline group.Hypertension was induced by subcutaneous infusion with angiotensinⅡ0.7 mg·kg-1·d-1for 2 weeks by osmotic mini-pumps in rats.Hydrogen-rich saline(10 mL·kg-1·d-1)was administered by intraperitoneal injection for 14 d.Platelet adhesion on collagen surface was evaluated using a well-defined perfusion chamber at low shear rate(300s-1)and high shear rate(1080s-1).The maximum aggregation rate of platelets induced by ADP was determined by turbidimetry.The levels of reactive oxygen species(ROS),nitric oxide(NO)and Ca2+in platelets were measured with flow cytometry.RESULTS When compared with the control group,platelet aggregation,platelet adhesion rate in high shear rate and low shear rate,and the level of ROS and Ca2+in platelets were elevated in hypertensive group.However,NO level in platelets decreased.Compared with the hypertensive group,hydrogen-rich saline treatment decreased platelet aggregation,platelet adhesion rate,the levels of ROS and Ca2+in platelets,and increased NO level in platelets of hypertensive rats.CONCLUSION Hydrogen-rich saline could inhibit platelet activation in hypertensive rats.This effect may be related to antioxidative stress.展开更多
Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hyp...Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hypertension （PAH） and discuss the underlying mechanisms preliminarily. Methods A classical PAH animal model was used, which was established by single injection of 50 mg · kg^-1 monocrotaline （MCT）. One week later, the rats were administrated with 1, 3, 10 mg · kg^-1 DL0805-2 via intraperitoneal injection for 18 days. At the end of the experiment, the body weight and survival rate were recorded. Meanwhile, the respiration function, heart function, blood pressure and pulmonary artery pressure were detected. Serum was collected for biochemical index analysis. The weight of vital organs was used to calculate the organ index. Histopathology examination was em-ployed to observe the subtle changes in hearts, vessels and lungs. Furthermore, the mechanisms were studied main- ly by the method of western blotting. Results DL0805-2 did not show significant influence on body weight of PAH rats. But the survival rate of PAH rats treated with 3 and 10 mg · kg^-1 DL0805-2 was increased up to 90. 9% com- pared with the model group （68.2%）. DL0805-2 improved the pulmonary artery blood flow especially the maximal -1 -1 velocity （PV max） from 397.2 cm · s^-1 to 506.5, 540. 1 and 574.0 cm · s^-1 respectively. The results of echocar- diography and electrocardiogram show that DL0805-2 had little effect on left ventricle and systemic circulation but attenuated right ventricle injury and decreased the right ventricle pressure from 73.73 mmHg to 47.80, 42.64 and 46.45 mmHg respectively after DL0805-2 intervention. Disease markers of PAH including NT-proBNP in serum and ET-1 in lung tissue homogenate and serum biochemical indicators, ALT, AST and LDH, were reduced by DL0805-2. DL0805-2 also relieved edema of lungs and decreased inflammatory cytokines production. Through the examination on histopathologic slide of pulmonary main artery, right ventricle and lung, DL0805 derivatives were found to have significant protection effect on structural changes of organs induced by pulmonary hypertension. Ac- cording to the preliminary study on the mechanisms of DL0805-2 in PAH, Rho/ROCK pathway was significantly in- hibited by DL0805 derivatives. In addition, DL0805 derivatives showed effect on BMPRII/p-Smad pathway and ap- optosis related pathway. Conclusion DL0805-2 has showed potent treatment effect on the PAH rats. And the un- derlying mechanisms studies also indicated that RhoA/ROCK and BMPRII pathways were involved. This work will provide basis experimental data for the further research and development of DL0805-2.展开更多
Adipose tissue plays pivotal roles in the development of hypertension,including white and brown adipocytes.Immunity and inflammation provide a bridge between adipose dysfunction and hypertensive target organ damage.We...Adipose tissue plays pivotal roles in the development of hypertension,including white and brown adipocytes.Immunity and inflammation provide a bridge between adipose dysfunction and hypertensive target organ damage.We firstly found that perivascular adipose tissue(PVAT)expressed abundant C3,which stimulated adventitial fibroblast migration and phenotype trans-differentiation.Subsequently,we showed that C5a regulated M1/M2 macrophage polarization and inhibited adiponectin production in the PVAT,which contributed to vascular inflammation in hypertension.展开更多
妊娠期高血压疾病(hypertensive disorders of pregnancy,HDP)是一类妊娠和血压升高并存的产科常见并发症,涵盖了妊娠期高血压(gestational hypertension,GH)、子痫前期(preeclampsia,PE)、妊娠合并慢性高血压(chronic hypertension)和...妊娠期高血压疾病(hypertensive disorders of pregnancy,HDP)是一类妊娠和血压升高并存的产科常见并发症,涵盖了妊娠期高血压(gestational hypertension,GH)、子痫前期(preeclampsia,PE)、妊娠合并慢性高血压(chronic hypertension)和慢性高血压并发子痫前期(chronic hypertension with superimposed pre-eclampsia)。这些疾病是导致孕产妇及围产儿死亡的主要原因之一。展开更多
2024年8月6日,上海交通大学公共卫生学院汪一心研究团队(Reproductive and Environmental Nexus for Extended Wellness,RENEW Lab)在J Hazard Mater在线发表题目为Blood trihalomethane and urinary haloacetic acid concentrations in...2024年8月6日,上海交通大学公共卫生学院汪一心研究团队(Reproductive and Environmental Nexus for Extended Wellness,RENEW Lab)在J Hazard Mater在线发表题目为Blood trihalomethane and urinary haloacetic acid concentrations in relation to hypertension:an observational study among 1162 healthy men的论文。该研究基于华中精子库队列,分析了饮用水消毒副产物三卤甲烷和卤代乙酸暴露对健康育龄男性血压的影响,并探讨了氧化应激的中介作用。研究发现血二氯一溴甲烷浓度升高显著增加1级和2级高血压发生风险。展开更多
罹患妊娠期高血压疾病（hypertensive disorders in pregnancy,HDP）的女性远期心血管疾病（cardiovascular disease,CVD）发病率远远高于无HDP病史的女性,且该差异在亚洲女性中尤为明显。大量研究发现,HDP女性子代中CVD及代谢性疾病发...罹患妊娠期高血压疾病（hypertensive disorders in pregnancy,HDP）的女性远期心血管疾病（cardiovascular disease,CVD）发病率远远高于无HDP病史的女性,且该差异在亚洲女性中尤为明显。大量研究发现,HDP女性子代中CVD及代谢性疾病发病率也显著升高,但母亲HDP与子代发生CVD之间的机制不明确,因而早期的针对性、个体化防控也无从谈起。展开更多
基金The project supported by the Natural Science Foundation of Anhui Provincial(1308085QH145)
文摘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.
文摘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.
文摘Aim To study the anti-hypertensive effect of total flavonoids of Cydonia oblonga Mill. in spontaneously hypertensive rats, then preliminarily investigate the mechanism of action based on anti-inflammatory function. Methods Total flavonoids of COM （COMF） were separated and purified by the optimal process, SHR were divid- ed into 6 groups as SHR control group （SHR）, captopril group （CAP, 25mg· kg^-1 · d^-1）, Eucommia ulmoides Oliver group （EUO, 30 mg · kg^-1· d^-1）, low （COMF-L, 40 mg · kg^-1· d^-1）, middle （COMF-M, 80 mg · kg^-1 · d^-1） and high dose （COMF-H, 160 mg · kg^-1· d ^-1） of COMF groups. 8 Wistar-Kyoto （WKY） rats were given distilled water instead as control. The drugs were given by intragastric administration for 16 weeks, then the levels of IL-1β, IL-6, IL-10, TNF-α and CRP in serum were tested. Results Compared with WKY group, the levels of IL-I~, IL-6, TNF-α and CRP were increased and IL-10 was decreased; Compared with SHR group, the levels of IL-1β, IL-6, TNF-α and CRP were decreased in COMF groups （P 〈0.01 or P 〈0.05） , while IL-10 was increased a little but without any significant difference （P 〈 0.05 ）. Conclusion Total flavonoids of Cydonia ob- longa Mill. showed the anti-hypertensive activity in spontaneously hypertensive rats and the mechanism was related to the function of anti-inflammatory.
文摘Objective Telomere length, as an emerging marker of biological age,isrelatedwithhypertension.Ouraimistoinvestigatethe relationship between telomere trajectory and blood pressure change as well as the incident cardiovascular events in a longitudinal hypertensive cohort in China.
文摘Objective To investigate the effects of simvastatin compared with standard treatment on cardiovascular outcomes and all-cause mortality in high-risk hypertensive patients with a high–normal level of total cholesterol(TC).Methods In a randomized,open-label,blinded-endpoint trial,hypertensive patients at high risk for cardiovascular events from 180 clinical centers in China were assigned to receive treatment with amlodipine plus amiloride/hydrochlorothiazide(n=6,776)or telmisartan(n=6,766).
基金National Natural Science Foundation of China(81860732)Scientific and Technological Projects for Social Development in Guizhou Province of China([2011]3036)the State Key Laboratory of Cardiovascular Disease(2017kf-03)
文摘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.
文摘Objective Recent evidence has indicated that hypertension is associated with impaired cognitive function. However, the prevention of cognitive disorders with antihypertensive therapy remains controversial.The trial provided evidence to compare the efficacy on cognitive function with the combination of amlodipine with diuretics or angiotensin II receptor blocker.
基金The project supported by National Natural Science Foundation of China(81274123,81374003)National Major Scientific and Technological Specialized Project for the Significant Formulation of New Drugs,China(2011ZX09101-002-07,2009ZX09502-016)
文摘OBJECTIVE Nowadays,with the living habits and diet structure changes,the morbidity and mortality of hypertension has been rising yearly,which induced by adverse lifestyles,excessive alcohol and poor diet.However,the animal models of hypertension resulted from adverse lifestyles have rarely been reported.It is essential to set up some more systematic models to study the characters of hypertension and evaluate the efficacy of traditional Chinese medicine(TCM).METHODS To build the rat model of human lifehabitual hypertension,SD rats had free access to alcohol with high-sucrose-fat diet(AHSFD),alcohol with high-fat diet(AHFD),high-sucrose-fat diet(HSFD),high-fat diet(HFD)and alcohol etc.Various of indicators were detected systematically to explore the features of hypertension models which included blood pressure(BP),liver and kidney functions,the lipid profiles and indexes quantifying TCM symptoms.Then we choose one of the stable and sustained animal models,studying the effects of RPA.E(which extracted from a TCM)on modulating the level of hypertension and the preliminary mechanism in this abstract.RESULTS ①The BP level,serum TC,TG,LDL-C of AHSFD-induced and AHFD-induced rats increased significantly,while the HDL-C reduced in the 4th week.② The BP level HSFD-induced rats increased significantly in the 6th week,serum TC,TG increased in 10 th week.③ The BP level of alcohol-induced rats increased significantly in the 9th week,serum TC,TG increased in 24 th week.④ The level of serum ALT,AST,UA and Cr of all model rats increased significantly after 12 weeks.Meanwhile the microcirculation increased significantly after8 weeks.⑤ After 4-week administration,RPA.E could significantly reduce BP of AHFD-induced hypertensive rats,and could reduce the serum TC,LDL-C,HDL-C,ALT,AST level after 8-week.CONCLUSION The rats induced by AHSFD,AHFD,HSFD and alcohol can raise BP obviously with underlying hepatic and kidney damage,the lipid profiles disorder and TCM symptoms change,while the AH(S)FD-induced hypertension models are earlier and more stable.RPA.E could mildly reduce BP level,and improve the lipid profiles disorders,hepatic damage,which reflects the characteristics of TCM on antihypertensive effects.The above models have their own characteristics,can be used to study the causes and pathogenesis of hypertension complicating metabolic disorder and the related treatment drug screening.
基金The project supported by National Natural Science Foundation of China(81374003)National Major Scientific and Technological Specialized Project for the Significant Formulation of New Drugs,China(2011ZX09101-002-07)Zhejiang province health high-level innovative talents training project
文摘OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,GSY,metoprolol or GSY combined with metoprolol for 4weeks.Blood pressure,which included SBP,DBP and MBP was measured by a noninvasive method every week.At the end of4 weeks,blood was drawn from the ophthalmic venous plexus to determine blood fat levels(serum TC,TG,LDL-c,HDL-c),liver function(serum ALT,AST),and kidney function(serum BUN,UA and Cr)by the ACCUTE(TBA-40FR)automatic.② The aortae of normal SD rats were prepared and cleaned from periadventitial fat and surrounding connective tissue and cut transversely into 4-mm width rings.To observe different concentration of GYS,metoprolol or GSY combined with metoprolol causing relaxation of the isolated aortic rings precontracted until a stable plateau by noradrenaline(NA)directly or in the presence of eNOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin(INDO)respectively.③ The concentrations of plasma GSY was determined by the HPLC after rats administered orally with GSY or GSY combined with metoprolol for single-dose.DAS data processing software calculated the pharmacokinetic parameters of GSY.RESULTS There was a significant synergism between GYS and metoprolol in lowering blood pressure and the concentrations of serum TC and LDL-c of SHR.The relaxant effect of GYS combined with metoprolol on the aortic rings precontracted by NA could be attenuated by L-NAME or INDO.The AUC0-tof GSY significantly increased after in conjunction with metoprolol.CONCLUSION GYS combined with metoprolol increases the concentrations of plasma GSY and synergistically lowers blood pressure based on endothelium-dependent vasodilatation function(EDVF).
基金The project supported National Natural Science Foundation of China(81173061)the Collaborative Innovation Center for Research and Development of Traditional Chinese Medicine in Mount Tai+2 种基金the Foundation of Overseas Distinguished Taishan Scholars of Shandong Province(FODTS)the Natural Science Foundation of Shandong Province(ZR2014HQ007)the Science and Technology Project of Taian City(201440774-25)
文摘OBJECTIVE To investigate the effect of hydrogen-rich saline on platelet activation in hypertensive rats.METHODS The male Wistar rats were divided into control group,hypertension group,control+hydrogen-rich saline group and hypertension+hydrogen-rich saline group.Hypertension was induced by subcutaneous infusion with angiotensinⅡ0.7 mg·kg-1·d-1for 2 weeks by osmotic mini-pumps in rats.Hydrogen-rich saline(10 mL·kg-1·d-1)was administered by intraperitoneal injection for 14 d.Platelet adhesion on collagen surface was evaluated using a well-defined perfusion chamber at low shear rate(300s-1)and high shear rate(1080s-1).The maximum aggregation rate of platelets induced by ADP was determined by turbidimetry.The levels of reactive oxygen species(ROS),nitric oxide(NO)and Ca2+in platelets were measured with flow cytometry.RESULTS When compared with the control group,platelet aggregation,platelet adhesion rate in high shear rate and low shear rate,and the level of ROS and Ca2+in platelets were elevated in hypertensive group.However,NO level in platelets decreased.Compared with the hypertensive group,hydrogen-rich saline treatment decreased platelet aggregation,platelet adhesion rate,the levels of ROS and Ca2+in platelets,and increased NO level in platelets of hypertensive rats.CONCLUSION Hydrogen-rich saline could inhibit platelet activation in hypertensive rats.This effect may be related to antioxidative stress.
文摘Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hypertension （PAH） and discuss the underlying mechanisms preliminarily. Methods A classical PAH animal model was used, which was established by single injection of 50 mg · kg^-1 monocrotaline （MCT）. One week later, the rats were administrated with 1, 3, 10 mg · kg^-1 DL0805-2 via intraperitoneal injection for 18 days. At the end of the experiment, the body weight and survival rate were recorded. Meanwhile, the respiration function, heart function, blood pressure and pulmonary artery pressure were detected. Serum was collected for biochemical index analysis. The weight of vital organs was used to calculate the organ index. Histopathology examination was em-ployed to observe the subtle changes in hearts, vessels and lungs. Furthermore, the mechanisms were studied main- ly by the method of western blotting. Results DL0805-2 did not show significant influence on body weight of PAH rats. But the survival rate of PAH rats treated with 3 and 10 mg · kg^-1 DL0805-2 was increased up to 90. 9% com- pared with the model group （68.2%）. DL0805-2 improved the pulmonary artery blood flow especially the maximal -1 -1 velocity （PV max） from 397.2 cm · s^-1 to 506.5, 540. 1 and 574.0 cm · s^-1 respectively. The results of echocar- diography and electrocardiogram show that DL0805-2 had little effect on left ventricle and systemic circulation but attenuated right ventricle injury and decreased the right ventricle pressure from 73.73 mmHg to 47.80, 42.64 and 46.45 mmHg respectively after DL0805-2 intervention. Disease markers of PAH including NT-proBNP in serum and ET-1 in lung tissue homogenate and serum biochemical indicators, ALT, AST and LDH, were reduced by DL0805-2. DL0805-2 also relieved edema of lungs and decreased inflammatory cytokines production. Through the examination on histopathologic slide of pulmonary main artery, right ventricle and lung, DL0805 derivatives were found to have significant protection effect on structural changes of organs induced by pulmonary hypertension. Ac- cording to the preliminary study on the mechanisms of DL0805-2 in PAH, Rho/ROCK pathway was significantly in- hibited by DL0805 derivatives. In addition, DL0805 derivatives showed effect on BMPRII/p-Smad pathway and ap- optosis related pathway. Conclusion DL0805-2 has showed potent treatment effect on the PAH rats. And the un- derlying mechanisms studies also indicated that RhoA/ROCK and BMPRII pathways were involved. This work will provide basis experimental data for the further research and development of DL0805-2.
文摘Adipose tissue plays pivotal roles in the development of hypertension,including white and brown adipocytes.Immunity and inflammation provide a bridge between adipose dysfunction and hypertensive target organ damage.We firstly found that perivascular adipose tissue(PVAT)expressed abundant C3,which stimulated adventitial fibroblast migration and phenotype trans-differentiation.Subsequently,we showed that C5a regulated M1/M2 macrophage polarization and inhibited adiponectin production in the PVAT,which contributed to vascular inflammation in hypertension.
文摘妊娠期高血压疾病(hypertensive disorders of pregnancy,HDP)是一类妊娠和血压升高并存的产科常见并发症,涵盖了妊娠期高血压(gestational hypertension,GH)、子痫前期(preeclampsia,PE)、妊娠合并慢性高血压(chronic hypertension)和慢性高血压并发子痫前期(chronic hypertension with superimposed pre-eclampsia)。这些疾病是导致孕产妇及围产儿死亡的主要原因之一。
文摘2024年8月6日,上海交通大学公共卫生学院汪一心研究团队(Reproductive and Environmental Nexus for Extended Wellness,RENEW Lab)在J Hazard Mater在线发表题目为Blood trihalomethane and urinary haloacetic acid concentrations in relation to hypertension:an observational study among 1162 healthy men的论文。该研究基于华中精子库队列,分析了饮用水消毒副产物三卤甲烷和卤代乙酸暴露对健康育龄男性血压的影响,并探讨了氧化应激的中介作用。研究发现血二氯一溴甲烷浓度升高显著增加1级和2级高血压发生风险。
文摘罹患妊娠期高血压疾病（hypertensive disorders in pregnancy,HDP）的女性远期心血管疾病（cardiovascular disease,CVD）发病率远远高于无HDP病史的女性,且该差异在亚洲女性中尤为明显。大量研究发现,HDP女性子代中CVD及代谢性疾病发病率也显著升高,但母亲HDP与子代发生CVD之间的机制不明确,因而早期的针对性、个体化防控也无从谈起。
