噻嗪类利尿剂对自发性高血压大鼠内皮型一氧化氮合酶和内皮素-1表达影响的研究

目的研究噻嗪类利尿剂治疗自发性高血压大鼠时对其内皮型一氧化氮合酶和内皮素-1表达的影响,从而探讨其降压的可能分子机制。方法15只自发性高血压大鼠随机分为3组,分别经胃管给予氢氯噻嗪(HCTZ,10 mg.kg-1.d-1)、吲哒帕胺(IND,0.625 mg.kg-1.d-1)和等量去离子水。每周测血压1次,4 wk后处死动物,分别用RT-PCR和W estern B lot法检测组织中内皮素-1和内皮型一氧化氮合酶mRNA和蛋白质的表达。结果氢氯噻嗪和吲哒帕胺用药1 wk后SHR的血压降低,2wk时降压幅度达到显著水平(P<0.05)。同时两种利尿剂均可在蛋白质水平上调内皮型一氧化氮合酶的表达,在mRNA水平下调内皮素-1的表达。结论噻嗪类利尿剂可能通过上调内皮型一氧化氮合酶及下调内皮素-1而起到调节血压与改善血管内皮功能作用。

Effects of thiazide diuretics on the gene expression of endothelial nitric oxide synthase and endothelin-1 in the spontaneous hypertensive rats

Aim To investigate the effects of thiazide diuretics on the gene expression of endothelial nitric oxide synthase(eNOS) and endothelin(ET-1) in the spontaneous hypertensive rats(SHRs),and to clarify molecular mechanisms of antihypertrension of thiazide diuretics.Method Fiveteen SHRs were divided randomly into 3 groups and administered orally once a day with HCTZ(10 mg·kg~(-1)),indapamide(0.62 5mg·kg~(-1)) and vehicle,respectively.Systolic blood pressure was observed weekly.After 4 weeks,the SHRs were sacrificed,and the levels of gene expression of eNOS and ET-1 were detected in tissures of SHRs.Results Both hydrochlorothiazide and indapamidecan reduced significantly blood pressure of SHRs,and also,up-regulated the expression of eNOS at protein level as well as down-regulate the expression of ET-1 at mRNA level.Conclusion Thiazide diuretics can reduce blood pressure through up-regulating the gene expression of eNOS and down-regulating the expression of ET-1.