Ruzicka M, Yuan B, Leenen F H
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
Circulation. 1994 Jul;90(1):484-91. doi: 10.1161/01.cir.90.1.484.
The role of nonhemodynamic cardiac trophic mechanisms differs not only between different models of cardiac hypertrophy but also within the same model for development versus maintenance of cardiac hypertrophy. Our previous studies pointed to a major role for the renin-angiotensin system (RAS) as a cardiac trophic stimulus in the remodeling of the heart in response to volume overload by aortocaval shunt or minoxidil treatment.
In the present study, we evaluated the effects of blockade of the RAS by the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II receptor blocker losartan on left ventricular (LV) and right ventricular mass and LV dilation in relation to changes in central hemodynamics during the maintenance of minoxidil and aortocaval shunt-induced cardiac hypertrophy. Both blockers similarly decreased LV end-diastolic pressure (LVEDP) and LV peak systolic pressure, whereas cardiac output remained unchanged in both models of volume overload. This suggests a major contribution of improved LV performance and decreased afterload to the decrease in cardiac preload by the two blockers rather than decreased venous return. Both blockers reversed LV hypertrophy in parallel to their effects on LVEDP in both models of volume overload. In minoxidil-treated rats, the extent of reversal in LV mass and dilation by the two blockers was similar to "spontaneous regression" after discontinuation of minoxidil treatment.
These results indicate that in contrast to the development phase of cardiac hypertrophy, the RAS does not contribute to the maintenance of volume overload-induced cardiac hypertrophy in these two models via direct cardiac trophic effects. The RAS, however, maintains cardiac hypertrophy indirectly by contributing to the persistence of high filling pressures.
非血流动力学心脏营养机制的作用不仅在不同的心脏肥大模型之间存在差异，而且在同一模型中，对于心脏肥大的发展与维持也有所不同。我们之前的研究指出，肾素-血管紧张素系统（RAS）作为一种心脏营养刺激因素，在因主动脉腔静脉分流或米诺地尔治疗导致容量超负荷时心脏重塑过程中发挥着主要作用。
在本研究中，我们评估了血管紧张素转换酶抑制剂依那普利和血管紧张素II受体阻滞剂氯沙坦对RAS的阻断作用，观察其对左心室（LV）和右心室质量以及LV扩张的影响，同时观察在米诺地尔和主动脉腔静脉分流诱导的心脏肥大维持过程中，这些影响与中心血流动力学变化之间的关系。两种阻滞剂均同样降低了LV舒张末期压力（LVEDP）和LV收缩压峰值，而在两种容量超负荷模型中，心输出量均保持不变。这表明，两种阻滞剂降低心脏前负荷主要是通过改善LV功能和降低后负荷，而非减少静脉回流。在两种容量超负荷模型中，两种阻滞剂均能逆转LV肥大，且与它们对LVEDP的影响平行。在米诺地尔治疗的大鼠中，两种阻滞剂使LV质量和扩张逆转的程度与米诺地尔停药后的“自发消退”相似。
这些结果表明，与心脏肥大的发展阶段不同，在这两种模型中，RAS并非通过直接的心脏营养作用来维持容量超负荷诱导的心脏肥大。然而，RAS通过促使高充盈压持续存在而间接维持心脏心脏肥大。
