Abstract:Aim To investigate the effects of zopiclone on patients of typeⅠessential hypertension combined with dyssomnia and explore its mechanism of action. Methods Patients with essential hypertension combined with dyssomnia were included and randomly assigned in two groups:non-drug treatment of patients were provided with lifestyle management advices including control of salt intake, physical exercise, prohibiting use of cigarettes and alcohols and improving food diversity; patients in the zopiclone group were given zopiclone along with the same lifestyle advices. The Pittsburgh Sleep Quality Index (PQSI), blood pressures (BPs), plasma renin activity (PRA), blood concentration of angiotension Ⅱ (AngⅡ) and aldosterone (ALD) before and after the treatment were compared. Results Zopiclone showed significant course-dependent effect of lowering PSQI and improving quality of sleep (P<0.05, P<0.01, respectively), the outcome of the zopiclone group was better than non-drug group (P<0.001). After 6 weeks’ therapy, SBP and DBP of the zopiclone group patients were lower than the non-drug group (P<0.05, P<0.01). Meanwhile, improvements in PRA, AngⅡ and ALD were more significant as well compared to the non-drug group (P<0.05, P<0.01). Conclusion Zopiclone is effective in controlling the blood pressures of patients with typeⅠessential hypertension combined with dyssomnia, and deactivating RAAS by improving sleep-disorder is possibly involved in its effects.

Abstract:Heart failure (HF) is the end stage of most cardiovascular diseases. Increasing evidence indicates that serum parathyroid hormone (PTH) is significantly elevated in patients with HF. Experimental studies confirm that there is a significant interaction between PTH, angiotensin Ⅱ and aldosterone, which may be involved in the pathogenesis of HF. This article reviews the relationship between PTH and HF and the possible mechanisms involved in the pathogenesis of HF, in order to accumulate the data of PTH as a new marker and clinical intervention target of HF.

Abstract:Aim To study renin-angiotensin-aldosterone system (RAAS) hormone levels and CYP11B2－344C/T gene polymorphism in essential hypertension patients with obesity, discuss genetic susceptibility of CYP11B2－344C/T genotype and the correlation between susceptible gene and RAAS levels.Methods 60 cases of patiens with 1～2 grade essential hypertension (30 cases essential hypertension patients with obesity, 30 cases essential hypertension patients without obesity), and 60 people from the Examination Center (30 cases obesity people without hypertension, 30 cases healthy people) were enrolled randomly. CYP11B2－344C/T gene polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism and agarose gel electrophoresis methods, plasma RAAS concentration were detected by radioimmunoassay.Results Multi-compared with number of cases of TT and TC＋ CC genotype, there were significant differences (P<0.05). And differences in essential hypertension with obesity group was the most significant multi-compared with the number of T and C alleles, significant differences were found (P<0.05), and differences in essential hypertension with obesity group was predominant. Plasma renin, angiotensin Ⅱ, aldosterone concentrations in genotype TT cases were much higher than those of TC and CC genotype (P<0.05), but there was no significant differences between CC and TC genotype cases (P>0.05).Conclusions In CYP11B2－344C/T gene polymorphism, TT genotype may be susceptible genotype of essential hypertension patients without obesity, and T allele may be susceptible one of them. Each component of plasma RAAS hormone levels in the TT genotype cases was significantly higher than the CC and the TC genotype ones.

Abstract:Aim To explore the inhibition of aldosterone(ALD)on proliferation of human umbilical vein endothelial cells(HUVEC)and its mechanism.Methods MTT was used to measure the proliferation.Flow cytometry assay(FCM)was applied for the detection of the apoptosis;Vascular Endothelial Growth Factor(VEGF)mRNA and VEGF protein were measured by semiquantitative RT-PCR and Western blot,respectively.Results ①Proliferation of HUVEC was inhibited by ALD in a dose-dependent manner,the cell viability of HUVEC decreased gradually.②However,when the concentration of ALD was above 800 μg/L,HUVEC were resistant to ALD.After the cells were incubated with ALD(800 μg/L)for 24 h.The rate of apoptosis in the HUVEC could reach 26.5%±3.3%.③The expression of VEGF mRNA and VEGF protein in HUVEC were decreased after it was incubated with ALD.Conclusion ALD can induce apoptosis and inhibit proliferation of HUVEC through changing the expression of VEGF.

Abstract:Aim To explore the influence of angiotensin-(1-7) [Ang-(1-7)] on the secretion of E-selectin(E-sel) and monocyte chemotactic protein-1(MCP-1) in cultured human umbilical vein cells induced by angiotensin Ⅱ(AngⅡ),and to clarify the antagonism of Ang-(1-7) on the inflammation induced by AngⅡ. Methods The cultured human umbilical vein endothelial cells(HUVECs) were randomly divided into control group,AngⅡ group,Ang-(1-7) group,Ang-(1-7)+AngⅡ group,and A-779+Ang-(1-7)+AngⅡ group.The expressions of E-sel and MCP-1 inprotein level and mRNA level were detected by enzyme linked immunosorbent assay(ELISA) and reverse transcription polymerase chain reaction(RT-PCR). Results ①Compared with the control group,100 nmol/L AngⅡ distinctly increased the protein of E-sel(25.39±1.97 μg/L) and MCP-1(238.71±5.51 ng/L) in HUVECs(P<0.01),and significantly increased mRNA expression of E-sel and MCP-1 in HUVECs(P<0.01).②Compared with the AngⅡ group,Ang-(1-7)(1 000 nmol/L) decreased the protein of E-sel(3.72±0.95 μg/L) and MCP-1(90.24±9.82 ng/L)(P<0.01),and the mRNA expression of E-sel and MCP-1(P<0.01).③10～10 000 nmol/L Ang-(1-7) attenuated the protein of E-sel in HUVECs induced by AngⅡ in a concentration dependent manner(21.15±1.31 μg/L,17.41±1.94 μg/L,12.71±1.84 μg/L and 9.46±1.40 μg/L)(P<0.01),and also inhibited the protein of MCP-1 in HUVECs induced by AngⅡ in a concentration dependent manner(214.57±7.16 ng/L,196.83±8.20 ng/L,176.63±8.93 ng/L and 155.52±8.19 ng/L)(P<0.01).④Compared with the AngⅡ group,10～10 000 nmol/L Ang-(1-7) inhibited the mRNA expression of E-sel and MCP-1 in HUVECs induced by AngⅡ in a dose dependent manner(P<0.01).⑤The A-779 group had no significant deviation than the AngⅡ group(P>0.05). Conclusions Ang-(1-7) inhibited the secretion of E-sel and MCP-1 in cultured HUVECs induced by AngⅡ in a concentration dependent matter.The inhibition effect of Ang-(1-7) may be through its specific receptor.

Abstract:Aim To study the relation of myocardial apoptosis and interstitial fibrosis in non-infarct zone during the subsequent stages after infarction and its mechanisms by setting up an infarcted model of rat. Methods 10-12 femal rats underwent sham operation or left coronary artery ligation, were killed after 24 h, 1 week, 2 weeks and 4 weeks of operation respectively. Left ventricular structure was observed by HE staining, Messon staining was used for the determination of collagen volume fraction (CVF), TUNEL was used for detection of apoptotic cells, radioimmunoassay was used for cardiac AngⅡ and Ald contents and reverse transcriptase-polymerase chain reaction (RT-PCR) for genes expression of collagen type 1 and collagen type 3. Results The infarction sizes were 24%-33%. From 7 days to 28 days after operation, the apoptotic cells and the apoptotic index increased, the Ang Ⅱ level increased gradually (p<0.05～0.001), collagen type 3 mRNA grey level was significantly higher in MI group (p<0.05). From 14 days to 28 days after operation, the CVF increased gradually along with the course of infarction (p<0.05～0.01), ALD level increased gradually and collagen type 1 mRNA grey level was markedly higher in MI group (p<0.05～0.01). Conclusions ①Apoptosis happened in non-infarct zone 14 days after MI in rats. ②There was interstitial fibrosis in non-infarct zone 14 days after MI in rats. ③The interstitial fibrosis might be associated with activation of cardiac RAAS. ④The apoptosis of cardiocytes in non-infarct zone might be related with the excess deposition of interstitial collagen.

Abstract:Aim To investigate the effect of aldosterone on expression of angiotensin Ⅱ type 1 (AT1) receptor in rat cardiac fibroblasts (CFs) and test the effect of aldosterone on AngⅡ induced collagen synthesis. Methods Cardiac fibroblasts culture were established from neonatal rats. Collagen synthesis was measured by 3 H proline incorporation after incubation with AngⅡ, aldosterone and AngⅡ plus aldosterone. The density of AT 1 recetpor was determined by 125 Ⅰ Ang Ⅱ saturation binding, and AT1 receptor mRNA levels were analyzed by quantitative reverse transcriptase polymerase chain reaction(RT PCR). Results AngⅡ increased collagen synthesis in cultured CFs; while aldosterone did not affect production of collagen. However, aldosterone could significantly potentiate the incremental effect of AngⅡ on collagen synthesis in CFs. The density of AT1 receptor inceased 2 fold and was accompanied by a 1.5 fold increase in the corresponding mRNA after treatment of aldosterone(10 -7 mol/L). Conclusion Aldosterone does not exert a direct effect on collagen synthesis in cultured rat CFs, but could influence the collagen output of CFs through the upregulated AT1 receptor.

Abstract:Aim To investigate the role of angiotensin Ⅱ(AngⅡ) 1 type recepter antagonist and aldosterone (Ald) receptor antagonist in reversing myocardial remodeling in hypertensive rats by blocking renin angiotensin system at receptor level and the mechanism of hypertensive myocordial remodeling. Methods Thirty nine male Wistar rats were devided into the shamo operated group, the hypertension group, the valsartan group [10 μg/(kg·d)] and spironolactone group [40 mg/(kg·d)]. Systolic blood pressure (SBP), left ventricular weight index (LVWI), plasma and myocardial AngⅡ/Ald concentration, myocardial collagen concentration (MCC) and collagen volume fraction (CVF) were measured at the sixteenth week, the twentieth week and the twenty eighth week after operation. The pathologic characterization of myocardial Ⅰ type and Ⅲ type collagen was observed at the same time. Results All measured datas in 2K1C hypertension group were significantly higher than in shamo operated group (p<0.05 or 0.005). Compared with hypertension group, plasma AngⅡ concentration was significantly higher (p<0.05), but SBP, LVWI, MCC mainly Ⅰ type collagen, CVF and plasma Ald concentration in the valsartan group decreased significantly (p<0.05). Treatment with spironolactone lightly decreased SBP, LVWI, MCC and CVF in early, but significantly lowered LVWI, MCC and CVF (p<0.05), especially Ⅲ type collagen. Conclusions It indicated that development of the LVH and myocardial fibrosis is heterochronia. This study suggested AngⅡ and aldsterone play a vital role in hypertensive myocardial remodeling. AT 1 receptor mainly mediats type I collagen deposition while aldosterone receptor mainly mediates type Ⅲ collagen deposition.

Abstract:Aim To investigate the role of angiotensinⅡ(AngⅡ) and aldosterone (Ald) in myocardial hypertrophy and fibrosis in hypertensive rats by blocking renin angiotensin system at receptor level. Methods Thirteen 2 kidney 1 clip (2K1C) hypertensive rats began to be administered valsartan in the drinking water (10 μg/g·d) at the sixteenth week after operation. Nineteen 2K1C rats were used as untreated controls. Nineteen sham operated rats were also used as controls. Systolic blood pressure (SBP), left ventricular weight index (LVWI), plasma and myocardial AngⅡ /Ald concentration, myocardial collagen concentration (MCC) and collagen volume fraction (CVF) were measured when three groups rats were killed at the sixteenth week, the twentieth week and the twenty eighth week after operation. Results All measured facts in 2K1C hypertensive group were significantly higher than in sham operated group (P<0.05 or 0.005). Compared with age matched 2K1C group, plasma AngⅡ concentration was higher significantly(P<0.05), but SBP, LVWI, MCC, CVF and plasma Ald concentration in treated group decreased significantly (P<0.05). Conclusions Left ventricular myocardial remodeling in renovascular hypertensive rats was closely related to myocardial AngⅡ and Ald concentration. Ang Ⅱ 1 (AT 1) receptor antagonist valsartan can block the pathophysiological effects of AngⅡ, inhibit Ald secretion and reveres left ventricular remodeling (mainly decrease deposition of type Ⅰ collagen). It suggests that AT 1 receptors may mediate the biological effects of AngⅡ in local tissue.