Brilla C G, Pick R, Tan L B, Janicki J S, Weber K T
Cardiovascular Institute, Michael Reese Hospital, University of Chicago Pritzker School of Medicine, Ill.
Circ Res. 1990 Dec;67(6):1355-64. doi: 10.1161/01.res.67.6.1355.
Pathological left ventricular hypertrophy in renovascular hypertension is associated with the accumulation of fibrillar collagen within the extracellular space and around intramyocardial coronary arteries. Even though the angiotensin converting enzyme inhibitor captopril was previously found to attenuate this interstitial and perivascular fibrosis, the relative importance of arterial and ventricular systolic pressures versus circulating angiotensin II (AII) and aldosterone (AL) in promoting hypertrophy and collagen accumulation in renovascular hypertension is uncertain. By drawing on the in-parallel arrangement of the right and left ventricles, with respect to their coronary circulation, and the in-series mechanical alignment of the ventricles, with a pressure-overloaded left and a normotensive right ventricle, this study sought to address this uncertainty. Three models of experimental hypertension, each having a different circulating AII and AL profile, were examined and compared with their controls: renovascular hypertension, where both AII and AL are increased; infrarenal aorta banding, where AII and AL are normal; and a chronic infusion of AL, where AII is suppressed or normal and AL is increased. In renovascular hypertension, as well as with AL, we found a significant rise in the interstitial collagen volume fraction and perivascular collagen area of the pressure-overloaded, hypertrophied left ventricle as well as the normotensive, nonhypertrophied right ventricle. This remodeling was not seen in either ventricle with infrarenal aorta banding despite comparable systemic hypertension and left ventricular hypertrophy. Thus, in experimental arterial hypertension in the rat, myocyte and nonmyocyte compartments of the myocardium are under separate controls: myocyte hypertrophy is most closely related to ventricular loading while circulating AII and AL, acting alone or in concert with other humoral factors, regulate the accumulation of collagen within the right and left ventricles.
肾血管性高血压所致的病理性左心室肥厚与细胞外间隙及心肌内冠状动脉周围的纤维状胶原积聚有关。尽管之前发现血管紧张素转换酶抑制剂卡托普利可减轻这种间质和血管周围纤维化,但在肾血管性高血压中,动脉压和心室收缩压相对于循环中的血管紧张素II(AII)和醛固酮(AL)在促进肥厚和胶原积聚方面的相对重要性尚不确定。通过利用左右心室在冠状动脉循环方面的平行排列,以及心室在机械方面的串联排列,即压力负荷过重的左心室和血压正常的右心室,本研究旨在解决这一不确定性。研究检查了三种实验性高血压模型,并将其与各自的对照组进行比较,每种模型具有不同的循环AII和AL特征:肾血管性高血压,其中AII和AL均升高;肾下主动脉缩窄,其中AII和AL正常;以及慢性输注AL,其中AII被抑制或正常而AL升高。在肾血管性高血压以及AL作用的情况下,我们发现压力负荷过重、肥厚的左心室以及血压正常、未肥厚的右心室的间质胶原体积分数和血管周围胶原面积均显著增加。尽管存在相当的全身性高血压和左心室肥厚,但在肾下主动脉缩窄的任一心室中均未观察到这种重塑。因此,在大鼠实验性动脉高血压中,心肌的心肌细胞和非心肌细胞部分受不同的控制:心肌细胞肥厚与心室负荷最密切相关,而循环中的AII和AL单独或与其他体液因子共同作用,调节左右心室内胶原的积聚。