Ruzicka M, Keeley F W, Leenen F H
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
Circulation. 1994 Oct;90(4):1989-96. doi: 10.1161/01.cir.90.4.1989.
Besides cardiac load, the renin-angiotensin system (RAS) and aldosterone may regulate collagen accumulation during maturation or hypertrophic growth. The effect of cardiac volume overload on both left ventricular (LV) and right ventricular (RV) collagen and elastin and the possible role of the RAS in such changes have not yet been assessed.
In the present study we assessed (1) the effects of 4 to 10 weeks of volume overload by an aortocaval shunt or minoxidil on LV and RV collagen and elastin and (2) the potential of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II receptor blocker losartan to prevent and regress volume overload-induced changes in cardiac collagen and elastin. Cardiac volume overload by aortocaval shunt or minoxidil treatment decreased LV collagen accumulation as compared with control rats. In contrast, RV collagen accumulation was potentiated during the initial weeks but not during chronic aortocaval shunt. Enalapril and losartan prevented the relative decreases in LV collagen content and concentration induced by a shunt. Losartan also reversed the decrease in LV collagen content by aortocaval shunt. Neither blocker significantly affected the enhanced RV collagen accumulation during the initial weeks of shunt, but both blockers further potentiated RV collagen accumulation during chronic volume overload. Aortocaval shunt for 4 weeks but not 10 weeks enhanced LV and RV elastin accumulation. This initial increase in LV and RV elastin content was blocked by both enalapril and losartan.
Cardiac volume overload, even when accompanied by increased plasma renin activity, decreases LV collagen accumulation, suggesting that in contrast to the stimulatory effect of systolic wall stress, increased diastolic wall stress inhibits collagen accumulation. In support of this concept, enalapril and losartan decreased LV preload and maintained LV collagen accumulation. In contrast to LV collagen, RV collagen accumulation was potentiated during the initial weeks of volume overload, possibly related to acute RV pressure overload shortly after aortocaval shunt and its decrease with chronic shunt. Enalapril and losartan had minimal effect on the enhanced RV collagen during the initial weeks of aortocaval shunt but potentiated RV collagen during chronic shunt, possibly by decreasing RV diastolic pressures. Altogether, these data suggest that during cardiac volume overload, the RAS affects cardiac collagen primarily by its hemodynamic effects. The RAS, however, may potentiate RV and LV elastin accumulation during the initial weeks of volume overload since both enalapril and losartan block this increase.
除心脏负荷外，肾素-血管紧张素系统（RAS）和醛固酮可能在心肌成熟或肥厚生长过程中调节胶原蛋白的积聚。心脏容量超负荷对左心室（LV）和右心室（RV）胶原蛋白和弹性蛋白的影响以及RAS在这些变化中可能发挥的作用尚未得到评估。
在本研究中，我们评估了：（1）通过主动脉腔静脉分流术或米诺地尔进行4至10周容量超负荷对左心室和右心室胶原蛋白和弹性蛋白的影响；（2）血管紧张素转换酶抑制剂依那普利和血管紧张素II受体阻滞剂氯沙坦预防和逆转容量超负荷引起的心脏胶原蛋白和弹性蛋白变化的潜力。与对照大鼠相比，通过主动脉腔静脉分流术或米诺地尔治疗引起的心脏容量超负荷降低了左心室胶原蛋白的积聚。相比之下，右心室胶原蛋白的积聚在最初几周有所增强，但在慢性主动脉腔静脉分流期间没有增强。依那普利和氯沙坦预防了分流引起的左心室胶原蛋白含量和浓度的相对降低。氯沙坦还逆转了主动脉腔静脉分流引起的左心室胶原蛋白含量的降低。两种阻滞剂在分流最初几周均未显著影响右心室胶原蛋白积聚的增强，但在慢性容量超负荷期间，两种阻滞剂均进一步增强了右心室胶原蛋白的积聚。4周而非10周的主动脉腔静脉分流增强了左心室和右心室弹性蛋白的积聚。依那普利和氯沙坦均阻断了左心室和右心室弹性蛋白含量的这种初始增加。
心脏容量超负荷，即使伴有血浆肾素活性增加，也会降低左心室胶原蛋白的积聚，这表明与收缩期壁应力的刺激作用相反，舒张期壁应力增加会抑制胶原蛋白的积聚。支持这一概念的是，依那普利和氯沙坦降低了左心室前负荷并维持了左心室胶原蛋白的积聚。与左心室胶原蛋白不同，右心室胶原蛋白的积聚在容量超负荷的最初几周有所增强，这可能与主动脉腔静脉分流后不久的急性右心室压力超负荷及其随慢性分流的降低有关。依那普利和氯沙坦在主动脉腔静脉分流最初几周对增强的右心室胶原蛋白影响最小，但在慢性分流期间增强了右心室胶原蛋白的积聚，可能是通过降低右心室舒张压。总之，这些数据表明，在心脏容量超负荷期间，RAS主要通过其血流动力学效应影响心脏胶原蛋白。然而，在容量超负荷的最初几周，RAS可能会增强右心室和左心室弹性蛋白的积聚，因为依那普利和氯沙坦均阻断了这种增加。
