Ruzicka M, Skarda V, Leenen F H
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
Circulation. 1995 Dec 15;92(12):3568-73. doi: 10.1161/01.cir.92.12.3568.
Cardiac volume overload by an aortocaval shunt increases left ventricular end-diastolic pressure (LVEDP) and plasma and cardiac renin activity and results in LV hypertrophy. To a similar extent, the angiotensin-converting enzyme (ACE) inhibitors enalapril and quinapril prevent the increase in LVEDP. However, only quinapril attenuates the development of LV hypertrophy. We hypothesize that a low affinity of enalapril for cardiac ACE results in continuing generation of cardiac angiotensin II and thus hypertrophic growth of cardiomyocytes.
In the present study, we assessed plasma and cardiac angiotensins I and II 1 and 7 days after aortocaval shunt and the effects of enalapril and quinapril started 3 days before surgery on plasma and cardiac angiotensin I and II at the same time points. Aortocaval shunt increased plasma angiotensin II at 1 day by 180%, but only a small increase (by 40%) persisted at 7 days. Aortocaval shunt increased LV angiotensin II by 100% and 65% at 1 and 7 days, respectively. Both blockers similarly prevented the increase in plasma angiotensin II by aortocaval shunt at both time points. In contrast, only quinapril prevented the rise in LV angiotensin II induced by shunt at 1 and 7 days.
Aortocaval shunt increases LVEDP and plasma and cardiac angiotensin II and results in LV hypertrophy. Only prevention of the increase in LVEDP and in plasma and cardiac angiotensin II attenuates the development of LV hypertrophy, consistent with the concept that angiotensin II is involved in the development of cardiac hypertrophy by aortocaval shunt by both hemodynamic and cardiac trophic effects. This study is the first to show that differences in affinity for cardiac ACE may determine the effect of ACE inhibitors on cardiac angiotensin II and therefore cardiac hypertrophy.
主动脉腔静脉分流导致的心脏容量超负荷会增加左心室舒张末期压力（LVEDP）以及血浆和心脏肾素活性，并导致左心室肥厚。在相似程度上，血管紧张素转换酶（ACE）抑制剂依那普利和喹那普利可防止LVEDP升高。然而，只有喹那普利能减轻左心室肥厚的发展。我们推测依那普利对心脏ACE的低亲和力导致心脏血管紧张素II持续生成，从而引起心肌细胞肥大性生长。
在本研究中，我们评估了主动脉腔静脉分流术后1天和7天血浆及心脏中的血管紧张素I和II，以及术前3天开始使用依那普利和喹那普利对相同时间点血浆及心脏血管紧张素I和II的影响。主动脉腔静脉分流使1天时血浆血管紧张素II增加180%，但在7天时仅持续有小幅增加（40%）。主动脉腔静脉分流使左心室血管紧张素II在1天和7天时分别增加100%和65%。两种阻滞剂在两个时间点均同样能防止主动脉腔静脉分流引起的血浆血管紧张素II升高。相比之下，只有喹那普利能在1天和7天时防止分流诱导的左心室血管紧张素II升高。
主动脉腔静脉分流增加LVEDP以及血浆和心脏血管紧张素II，并导致左心室肥厚。只有防止LVEDP以及血浆和心脏血管紧张素II升高才能减轻左心室肥厚的发展，这与血管紧张素II通过血流动力学和心脏营养作用参与主动脉腔静脉分流所致心脏肥厚发展的概念一致。本研究首次表明，对心脏ACE亲和力的差异可能决定ACE抑制剂对心脏血管紧张素II的作用，进而决定对心脏肥厚的作用。
