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标题：Effects of Losartan, an Angiotensin II Antagonist, on the Development of Cardiac Hypertrophy Due to Volume Overload
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作者：Masayuki ISHIYE ; Kazuo UMEMURA ; Toshihiko UEMATSU 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1995
卷号：18
期号：5
页码：700-704
DOI：10.1248/bpb.18.700
出版社：The Pharmaceutical Society of Japan
摘要：To investigate the contribution of a cardiac renin-angiotensin system to cardiac hypertrophy due to volume overload, the effects of losartan, a non-peptide angiotensin (Ang) II type 1 (AT₁) receptor antagonist, on left ventricular hypertrophy (LVH) was studied. LVH was produced in male Wistar rats by volume overload secondary to aortic insufficiency (AI). Losartan (10 mg/kg/d) was orally administered for 2 weeks after surgery to both AI and sham-operated (control) rats. Two weeks after surgery, aortic pulse pressure and left ventricular (LV) weight were markedly increased in the AI rats as compared with the control group, whereas cardiac angiotensin converting enzyme (ACE) activity remained unchanged. The effects of the chronic administration of losartan on AT₁ receptors were verified by the blockade of Ang II pressor response. Losartan treatment produced a significant reduction in LVH in AI rats without affecting the systolic blood pressure. In separate groups of rats, to elucidate the mechanisms of the attenuation of LVH by treatment with losartan, we determined plasma and LV immunoreactive Ang II content and plasma renin activity (PRA). LV Ang II content increased in AI rats, while plasma Ang II content, PRA and serum ACE activity did not. Losartan significantly reduced the LV Ang II content, whereas PRA and plasma Ang II concentration were increased by the treatment. There was a significant positive correlation between LV weight and LV Ang II content. These results suggest that cardiac Ang II, rather than circulating Ang II, plays an important role in the LVH due to volume overload via the AT₁ receptor.
关键词：cardiac hypertrophy;volume overload;angiotensin II;losartan