氢氯噻嗪对大鼠血压及肾素-血管紧张素系统活性物质水平的影响

Effects of hydrochlorothiazide on blood pressure and active substance level of renin-angiotensin system in rats

目的探讨氢氯噻嗪对SD大鼠血压和循环及心脏局部肾素-血管紧张素系统(RAS)活性物质水平的影响。方法取清洁级健康雄性SD大鼠128只,适应性喂养2周后随机分为对照组和实验组各64只。实验组大鼠每日给予氢氯噻嗪10 mg/kg灌胃,对照组每日给予相同容积的蒸馏水灌胃。连续灌胃4周后用鼠尾测压仪测量2组大鼠血压,处死后采用酶联免疫吸附实验检测血浆肾素活性(PRA)、血浆血管紧张素Ⅱ(AngⅡ)水平、心肌组织中AngⅡ水平,采用紫外分光法检测血清血管紧张素转换酶(ACE)活性,采用RT-PCR法检测心肌组织中AngⅡ1型受体mRNA(AT1R mRNA)表达量。结果实验组大鼠血压显著低于对照组(P<0.05);实验组大鼠血浆PRA活性、AngⅡ水平均明显高于对照组(P均<0.05),心肌组织中AT1R mRNA表达量明显低于对照组(P<0.05);2组血清ACE活性及心肌组织中AngⅡ水平比较差异均无统计学意义(P均>0.05)。结论氢氯噻嗪能有效降低大鼠的平均血压,在一定程度上影响循环RAS,并能下调心肌组织中AT1R mRNA的表达,可能具有一定程度的心肌保护作用。

Objective It is to investigate the effects of hydrochlorothiazide administrating on blood pressure,circulation and intracardiac renin-angiotensin system(RAS)in Sprague-Dawlay(SD)rats.Methods One hundred and twenty-eight clean-grade healthy male SD rats were taken,and after two weeks of adaptive feeding,they were randomly divided into 64 rats in the control group and 64 rats in the experimental group.The rats in the experimental group were given hydrochlorothiazide 10 mg/kg by gavage every day,and the ones in the control group were given the same volume of distilled water by gavage every day.After 4 weeks of continuous intragastric administration,the blood pressure of the rats in the two groups was measured with a rat-tail manometer.After the rats were sacrificed,the levels of plasma renin activity(PRA),plasma angiotensinⅡ(AngⅡ),and AngⅡin myocardial tissue were measured by enzyme-linked immunosorbent assay.The level of serum angiotensin-converting enzyme(ACE)activity was detected by ultraviolet spectroscopy,and the expression of AngⅡtype 1 receptor mRNA(AT1R mRNA)in myocardial tissue was detected by RT-PCR method.Results The blood pressure of the rats in the experimental group was significantly lower than that of the control group(P<0.05);the plasma PRA activity and AngⅡlevel of the experimental group were significantly higher than those of the control group(P<0.05),and the expression of AT1R mRNA in myocardial tissue was significantly lower than that of the control group(P<0.05).There was no significant difference in the serum ACE activity and the level of AngⅡin myocardial tissue between the two groups(P>0.05).Conclusion Administrating hydrochlorothiazide can significantly lower down the averaged blood pressure of rats,affect the circulating RAS to a certain extent,and can down-regulate the expression of AT1R mRNA in myocardial tissue,which may have a certain degree of myocardial protection.