Renin-angiotensin-aldosterone system and myocardial fibrosis.

Abstract

See article by Bishop et al. [26] (pages 57–67) in this issue. During the past decade, evidence has been provided that the circulating and local renin–angiotensin–aldosterone systems (RAAS) promote the development of myocardial fibrosis in hypertensive heart disease and chronic heart failure [1,2] including in vitro experiments using adult rat cardiac fibroblasts where both angiotensin II (AngII) [3–5] and aldosterone [3] stimulate collagen synthesis in a dose-dependent manner while AngII additionally suppresses the activity of matrix metalloproteinase 1, the key enzyme of interstitial collagen degradation [3], that synergistically leads to progressive collagen accumulation within the myocardial interstitium. This could be proved in in vivo studies in renovascular hypertension [1], with chronic administration of aldosterone [1,6,7], or in the spontaneously hypertensive rat (SHR) model of genetic hypertension [8–12] where a local cardiac AngII generating system is operative [13]. Therefore, the physiological role of RAAS on the development of myocardial fibrosis could be established. In particular, in various models of experimental hypertension with comparable degrees of elevated systolic arterial pressure and left ventricular hypertrophy (LVH), myocardial fibrosis was found only in the presence of stimulated circulating RAAS, i.e., in renovascular hypertension, or when aldosterone was chronically infused via subcutaneously implanted osmotic minipumps to raise plasma aldosterone levels as seen in congestive heart failure. There, interstitial and perivascular fibrosis was found in either ventricle, the pressure-overloaded, hypertrophied left ventricle and the non-overloaded, not hypertrophied right ventricle [1]. In contrast, myocardial fibrosis was absent in either ventricle of hypertensive rats with infrarenal aortic band where RAAS was not activated although LVH was present [1]. Furthermore, low output heart failure models, like rapid pacing in dogs, were associated with activation of RAAS and progressive increase in preload. There, myocardial fibrosis was seen in either ventricle [14]. On the … * Tel.: +49-6421-286-4980; fax: +49-6421-286-8954 brilla{at}t-online.de