Synergistic effects of ACE inhibition and Ang II antagonism on blood pressure, cardiac weight, and renin in spontaneously hypertensive rats
Synergistic effects of ACE inhibition and Ang II antagonism on blood pressure, cardiac weight, and renin in spontaneously hypertensive rats
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DOI：
10.1161/01.cir.96.9.3072
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发表时间：
1997-11-04
期刊：
影响因子：
37.8
通讯作者：
Gonzales, MF
中科院分区：
文献类型：
--
作者：
Menard, J;Campbell, DJ;Gonzales, MF
背景I型血管紧张素（Ang）II受体的阻断与ACE抑制相结合，可能会放大的功效的肾素-血管紧张素系统阻断，因为ACE抑制剂不完全和永久抑制血管紧张素II production.Methods和结果依那普利或氯沙坦（1，3，10，和30 mg/kg）或其组合给药2至4周自发性高血压大鼠。与相同或更高剂量的单药治疗相比，低剂量每种药物的组合诱导血压（BP）和左心室重量/体重（LVW/BW）比的降低幅度更大。当依那普利、氯沙坦及其组合的大致等效方案（根据BP下降判断）进行比较时，血浆和肾肾素以及血浆Ang-（1-7）和Ang I的升高相似，血浆血管紧张素原的降低相似。依那普利单独降低血浆Ang II水平，氯沙坦单独升高Ang II水平。依那普利与氯沙坦的组合防止或减少与losartanalsingle.Conclusions观察到的血管紧张素II水平的增加，这些研究结果表明，低剂量的依那普利和氯沙坦对BP和LVW/BW比的影响之间的协同作用是由于更有效地抑制肾素-血管紧张素系统的组合比任何单独的代理。当两种药物一起给药时，ACE拮抗剂诱导的血浆Ang II下降导致调节Ang II拮抗剂诱导的Ang II反应性升高，从而降低血浆Ang II浓度，其与拮抗剂竞争Ang II受体。
Background Blockade of type I angiotensin (Ang) II receptors combined with ACE inhibition may amplify the efficacy of the renin-angiotensin system blockade because ACE inhibitors do not completely and permanently suppress Ang II production.Methods and Results Enalapril or losartan (1, 3, 10, and 30 mg/kg) or their combination was administered for 2 to 4 weeks to spontaneously hypertensive rats. The combination of low doses of each agent induced greater reductions in blood pressure (BP) and left ventricular weight/body weight (LVW/BW) ratio than monotherapy with the same or higher doses. When approximately equipotent regimens of enalapril, losartan, and their combination, as judged by BP fall, were compared, there were similar increases in plasma and renal renin and in plasma Ang-(1-7) and Ang I and similar reductions in plasma angiotensinogen. Enalapril alone reduced plasma Ang II levels, and losartan alone increased Ang II levels. The combination of enalapril with losartan prevented or reduced the increase in Ang II levels observed with losartan alone.Conclusions These findings show that the synergistic interaction between the effects of low doses of enalapril and losartan on BP and LVW/BW ratio is due to more effective inhibition of the renin-angiotensin system by their combination than by either agent alone. When both drugs are given together, the ACE inhibitor-induced fall in plasma Ang II results in modulation of the Ang II antagonist-induced reactive rise in Ang II, thereby lowering the plasma Ang II concentration,which competes with the antagonist for the Ang II receptors.