Greater blood pressure-lowering effect of the renin inhibitor EMD 58265 than an angiotensin-converting enzyme inhibitor in two-kidney one-clip Goldblatt rabbit.
Greater blood pressure-lowering effect of the renin inhibitor EMD 58265 than an angiotensin-converting enzyme inhibitor in two-kidney one-clip Goldblatt rabbit.
复制标题
在两肾单夹 Goldblatt 兔中，肾素抑制剂 EMD 58265 的降血压效果优于血管紧张素转换酶抑制剂。
DOI：
10.1046/j.1440-1681.2000.03251.x
复制
发表时间：
2000
影响因子：
2.9
通讯作者：
Zimmerman,BG
中科院分区：
文献类型：
--
作者：
Zimmerman,BG
1. 肾素抑制剂在阻断肾素-血管紧张素系统（RAS）方面可能比血管紧张素转换酶（ACE）抑制剂或血管紧张素（Ang）拮抗剂更有利，因为它们不允许AngI或AngII在血浆中积累。2 .比较静脉给药两种人肾素抑制剂EMD 58265和u71038与ACE抑制剂依那普利拉对麻醉双肾一夹家兔平均血压（BP）、肾血流量（RBF）和血浆AngI、AngII的影响。在使用ACE抑制剂之前或之后，给药剂量为2-2.5 mg/kg，静脉注射EMD 58265和5-10 mg/kg，静脉注射u71038，这两种药物比依那普利特（2-4 mg/kg，静脉注射）降压约10 mmHg。在血压降低时，三种药物对RBF均无显著影响；然而，肾血管阻力降低。高剂量依那普利特（10mg /kg，静脉注射）对血压没有进一步的影响，但确实导致rbf显著增加。两种肾素抑制剂均显著降低血浆AngI，但高基础水平的AngII不太持续，仅受到轻微影响。依那普利特在低剂量和高剂量范围内也不能显著降低血管内皮素指数。结果表明，高循环AngII水平兔肾素抑制比ACE抑制更能有效降低血压。可能需要高剂量的ACE抑制剂来阻断肾内RAS，这可能是RBF增加的原因。
1. Renin inhibitors may be more advantageous than either angiotensin‐converting enzyme (ACE) inhibitors or angiotensin (Ang) antagonists in blocking the renin–angiotensin system (RAS) because they do not allow accumulation of either AngI or AngII in plasma.2. Effects of i.v. administration of two human renin inhibitors (EMD 58265 and U 71038) were compared with the ACE inhibitor enalaprilat on mean blood pressure (BP), renal blood flow (RBF) and plasma AngI and AngII in the anaesthetized two‐kidney one‐clip Goldblatt rabbit.3. At doses of 2–2.5 mg/kg, i.v., EMD 58265 and 5–10 mg/kg, i.v., U 71038, both drugs decreased BP approximately 10 mmHg more than enalaprilat (2–4 mg/kg, i.v.) when given either before or after the ACE inhibitor. None of the three agents had any significant effect on RBF in the face of the lowered BP; however, renal vascular resistance was decreased. A higher dose of enalaprilat (10 mg/kg, i.v.) had no further effect on BP than the lower doses but did cause a marked increase in RBF.4. Both renin inhibitors markedly decreased plasma AngI, but the high basal level of AngII was less consistently and only modestly affected. Enalaprilat, in either the low dose range or at the high dose, was also not effective in significantly decreasing AngII.5. The results indicate that renin inhibition in the rabbit with a high circulating AngII level is more effective in lowering BP than ACE inhibition. A high dose of the ACE inhibitor may be required to block the intrarenal RAS, which may account for the increase in RBF.