Roles of vascular angiotensin converting enzyme and chymase in two-kidney, one clip hypertensive hamsters
Roles of vascular angiotensin converting enzyme and chymase in two-kidney, one clip hypertensive hamsters
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DOI：
10.1097/00004872-199816050-00013
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发表时间：
1998-05-01
影响因子：
4.9
通讯作者：
Miyazaki, M
中科院分区：
文献类型：
--
作者：
Jin, D;Takai, S;Miyazaki, M
背景人类血管组织中存在食糜酶依赖性血管紧张素II形成途径；然而，食糜酶在高血压发病机制中的作用（如果有的话）尚不清楚。在研究食糜酶的作用时，重要的是要认识到物种间血管紧张素 II 形成系统的显着差异。我们最近发现仓鼠与人类一样也具有双重血管紧张素II形成系统。目的分析血管紧张素转换酶和糜酶在高血压发病中的潜在作用，进一步表征血管紧张素转换酶抑制剂和血管紧张素II受体拮抗剂治疗高血压的疗效。方法与结果双肾一夹仓鼠模型平均动脉压在夹闭后2周明显升高。 （急性期），4周后达到峰值，并维持在高水平，直到剪毛后32周（慢性期）。血浆肾素活性在急性期显着升高，但在慢性期恢复正常水平。剪毛后4-32周内血管紧张素转换酶活性显着高于对照仓鼠，相比之下，血管糜酶在整个实验期间没有激活。给予血管紧张素转换酶抑制剂群多普利和血管紧张素 II 受体拮抗剂 CV-11974，在急性和慢性阶段均能同等降低平均动脉压。 结论 血管紧张素转换酶在仓鼠两肾一夹高血压的维持中起主要作用，仓鼠与人类一样，拥有血管紧张素 II、血管糜酶的双重形成系统未参与仓鼠两肾一夹高血压的发病机制。 (C) 1998 年利平科特-乌鸦出版社。
Background A chymase-dependent angiotensin II-forming pathway is present in human vascular tissues; however, the role, if it plays any, of chymase in the pathogenesis of hypertension is not known. When investigating the role of chymase, it is important to recognize marked differences in vascular angiotensin II-forming systems among species. We found recently that hamsters, like humans, possess the dual angiotensin II-forming system.Objective To analyze the potential involvement of angiotensin converting enzyme and chymase in the pathogenesis of hypertension, and to further characterize the efficiency of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for the treatment of hypertension.Methods and results The mean arterial pressure in the two-kidney, one clip hamster model had increased significantly 2 weeks after clipping (acute stage), reached a peak after 4 weeks, and was sustained at the high level until 32 weeks after clipping (chronic stage). Plasma renin activity increased markedly during the acute stage, but returned to the normal level during the chronic stage. Vascular angiotensin converting enzyme activity during 4-32 weeks after clipping was significantly higher than that in the control hamsters, By contrast, vascular chymase was not activated throughout the experimental period. Administrations of an angiotensin converting enzyme inhibitor, trandolapril, and an angiotensin II receptor antagonist, CV-11974, equally lowered the mean arterial pressure during the acute and chronic stages.Conclusions Vascular angiotensin converting enzyme plays a predominant role in the maintenance of two-kidney, one clip hypertension in hamsters, which, like humans, possess a dual system of formation of angiotensin II, Vascular chymase was not involved in the pathogenesis of two-kidney, one clip hypertension in the hamster. (C) 1998 Lippincott-Raven Publishers.