Ferrario Carlos M, Smith Ronald D, Brosnihan Bridget, Chappell Mark C, Campese Vito M, Vesterqvist Ole, Liao Wei-chi, Ruddy Michael C, Grim Clarence E
Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Am J Hypertens. 2002 Jun;15(6):557-64. doi: 10.1016/s0895-7061(02)02268-9.
The contribution of angiotensin-(1-7) [Ang-(1-7)] to the antihypertensive actions of omapatrilat, a novel vasopeptidase inhibitor, was evaluated in 22 salt-sensitive, low renin, hypertensive subjects as a substudy of a multicenter randomized, double-blind, parallel study of 4 weeks duration. A total of 25 other subjects received lisinopril as the active control. Omapatrilat (40 mg) produced sustained control of blood pressure (BP) (as assessed by 24-h ambulatory BP measurements) that was significantly greater than that produced by 20 mg daily of lisinopril. The antihypertensive response to either drug was accompanied by similar sustained inhibition of angiotensin converting enzyme activity. Plasma levels of angiotensin I (Ang I), angiotensin II (Ang II) and Ang-(1-7) were not altered by treatment with either omapatrilat or lisinopril, even though both regimens produced a modest rise in plasma renin activity. In contrast, urinary excretion rates of Ang I and Ang-(1-7) but not Ang II increased significantly throughout the dosing period of subjects who were given omapatrilat, whereas the smaller antihypertensive response produced by lisinopril had a smaller and transient effect on increasing urinary excretion rates of Ang-(1-7). Omapatrilat, being a single molecule inhibiting neutral endopeptidase and converting enzyme simultaneously, controlled salt-sensitive hypertension by a mechanism that was associated with sustained increases in urinary Ang-(1-7) excretion. We suggest that Ang-(1-7) may be a component of the mechanisms by which omapatrilat induces an antihypertensive response in salt sensitive hypertension.
作为一项为期4周的多中心随机、双盲、平行研究的子研究，在22名盐敏感、低肾素高血压受试者中评估了血管紧张素 -（1 - 7）[Ang -（1 - 7）]对新型血管肽酶抑制剂奥美帕替的降压作用。另外共有25名受试者接受赖诺普利作为活性对照。奥美帕替（40毫克）产生了持续的血压（BP）控制（通过24小时动态血压测量评估），显著大于每日20毫克赖诺普利产生的血压控制效果。两种药物的降压反应均伴随着对血管紧张素转换酶活性的类似持续抑制。尽管两种治疗方案均使血浆肾素活性适度升高，但用奥美帕替或赖诺普利治疗均未改变血浆血管紧张素I（Ang I）、血管紧张素II（Ang II）和Ang -（1 - 7）的水平。相比之下，在接受奥美帕替的受试者给药期间，Ang I和Ang -（1 - 7）的尿排泄率显著增加，而Ang II未增加，而赖诺普利产生的较小降压反应对增加Ang -（1 - 7）的尿排泄率的影响较小且短暂。奥美帕替作为一种同时抑制中性内肽酶和转换酶的单一分子，通过与尿Ang -（1 - 7）排泄持续增加相关的机制控制盐敏感性高血压。我们认为，Ang -（1 - 7）可能是奥美帕替在盐敏感性高血压中诱导降压反应的机制的一个组成部分。
