Renin- and non-renin-mediated antihypertensive actions of converting enzyme inhibitors.
Renin- and non-renin-mediated antihypertensive actions of converting enzyme inhibitors.
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肾素和非肾素介导的转化酶抑制剂的抗高血压作用。
DOI：
10.1038/ki.1984.119
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发表时间：
1984
影响因子：
19.6
通讯作者：
Zusman,RM
中科院分区：
文献类型：
--
作者：
Zusman,RM
讨论 DR. RANDALL M. ZUSMAN（马萨诸塞州总医院心脏科高血压科主任，马萨诸塞州波士顿哈佛医学院医学助理教授）：今天讨论的这位患者为我们提供了一个机会来研究肾素-血管紧张素级联抑制剂的治疗效用。我将重点关注转换酶抑制剂的作用机制，并将提供卡托普利（一种口服活性转换酶抑制剂）的前列腺素依赖性、非肾素介导的抗高血压作用的证据。然而，在讨论这些问题之前，我想回顾一下目前对肾素-血管紧张素系统的认识。 肾素-血管紧张素级联 血管紧张素 II 刺激血管平滑肌并引起血管收缩。它还刺激肾上腺并导致醛固酮产生增加和继发性钠潴留。由于血管收缩和钠潴留都会增加血压，因此人们对临床上有用的肾素-血管紧张素级联抑制剂的开发给予了相当多的关注。如图 2 所示，血管紧张素 II 生成或其细胞作用的三个步骤可能受到攻击 [1]。肾素是一种主要由肾小球旁装置产生的蛋白水解酶，它裂解血管紧张素原（一种由肝脏合成的多肽），产生血管紧张素 I，它没有血管加压活性。血管紧张素转换酶主要位于肺循环内[21]，然后从血管紧张素I分子中去除两个氨基酸并形成八肽血管紧张素11；后一种化合物通过与其受体相互作用，收缩平滑肌并刺激醛固酮生物合成。抑制肾素-血管紧张素原反应、阻断血管紧张素II受体或抑制转化酶会减弱血管紧张素II在体内的生理作用，理论上应该会降低高血压实验模型和肾素依赖性高血压患者的血压。
DiscussionDR. RANDALL M. ZUSMAN (Director, Hypertension Division, Cardiac Unit, Massachusetts General Hospital, and Assistant Professor of Medicine, Harvard Medical School, Boston, Mass.): The patient presented for discussion today provides an opportunity for us to examine the therapeutic utility of inhibi-tors of the renin-angiotensin cascade. I will focus on the mechanism of action of the converting enzyme inhibitors and will present evidence for a prostaglandin-dependent, non-renin-mediated, antihypertensive effect of captopril, an orally active converting enzyme inhibitor. Before discussing these issues, however, I would like to review the present understanding of the renin-angiotensin system.Renin-angiotensin cascade Angiotensin II stimulates vascular smooth muscle and causes vasoconstriction. It also stimulates the adrenal gland and causes increased aldosterone production and secondary sodium retention. Because both vasoconstriction and sodium retention increase blood pressure, considerable attention has been directed toward the development of a clinically useful inhibitor of the renin-angiotensin cascade. As shown in Figure 2, three steps in the generation of angiotensin II or its cellular action can be attacked [1]. Renin, a proteolytic enzyme produced principally by the juxtaglomerular apparatus, cleaves angiotensinogen, a polypeptide synthesized by the liver, to produce angiotensin I, which has no vasopressor activity. The angiotensin converting enzyme, located principally within the pulmonary circulation [21, then removes two amino acids from the angiotensin I molecule and forms the octapeptide angiotensin 11; the latter compound, through interaction with its receptor, constricts smooth muscle and stimulates aldosterone biosynthesis. Inhibi-tion of the renin-angiotensinogen reaction, blockade of the angiotensin II receptor, or inhibition of converting enzyme diminishes the physiologic effect of angiotensin II in vivo and theoretically should decrease blood pressure in experimental models of hypertension and in patients with renin-dependent hypertension.