THE RENIN-ANGIOTENSIN SYSTEM IN THE HEART AND VASCULAR WALL - NEW THERAPEUTIC ASPECTS

Traditionally, the renin-angiotensin system (RAS) has been viewed as a n endocrine system. Recently, independent tissue RASs have been postul ated that are believed to act in a paracrine/autocrine fashion. Elemen ts of the RAS have been shown to exist in many peripheral tissues. Ang iotensin-converting enzyme (ACE), a key element of the RAS, is found m ainly in the vascular endothelium and therefore represents the main ta rget site for inhibition of the local and circulating RASs. In the hea rt, angiotensin II exerts a direct positive inotropic and chronotropic effect. More recently, it was also found that angiotensin II may act as a growth factor in several cell types. Angiotensin II is also thoug ht to be partially responsible for structural remodeling in cardiac hy pertrophy. The role of ACE inhibitors has been established in the trea tment of hypertension and congestive heart failure. Recent multicenter trials revealed a beneficial role of ACE inhibitors in reduction of m ortality rates in patients with congestive heart failure and a low eje ction fraction. Mechanisms that include reduction of myocardial oxygen demand, improvement of coronary blood flow, induction of capillary pr oliferation, reduction of blood pressure and ventricular wall tension without reflex tachycardia, and impairment of myocardial contractility are the basis for the beneficial effects of ACE inhibitors. In additi on to a reduction of angiotensin II generation, these effects appear t o be largely brought about by the inhibition of endogenous kinin degra dation. Recent studies suggest that a deletion polymorphism in the gen e encoding ACE is a risk factor in myocardial infarction (MI). In the future, ACE genotyping might identify patients in whom ACE-inhibitor t reatment is most likely to prevent MI.