Role of angiotensin II in the transition of left ventricular hypertrophy to cardiac failure

The transition from compensated to decompensated left ventricular hypertrophy can be precipitated by progression of structural or functional alterations of the myocardium, as well as activation of peripheral mechanisms that exacerbate clinically evident heart failure. The renin angiotensin system may be involved in both cardiac and peripheral adaptations that accelerate this detrimental process. Indeed, recent studies strongly suggest an activation of the cardiac renin angiotensin system in compensated cardiac hypertrophy, whereas both the circulating as well as the cardiac system may contribute to elevated angiotensin II levels in the decompensated state of left ventricular hypertrophy. Furthermore, left ventricular hypertrophy may be facilitated by genetic disposition in some individuals who display a slightly elevated 'basal tone' of the renin angiotensin system. Angiotensin II may be released by cardiac myocytes after imposition of mechanic stress. Local cardiac angiotensin II has been shown to be a potent growth stimulus for cardiac myocytes and fibroblasts. Taken together, increasing evidence suggests that angiotensin II is an important part of the signaling cascade resulting in the hypertrophic response of pressure overloaded hearts. In addition to these growth responses, cardiac function of the hypertrophied heart may be affected by angiotensin II. In particular, diastolic dysfunction - often the first signal for the transition to cardiac failure - may be related to the activated cardiac renin angiotensin system. Finally, angiotensin II contributes to increased peripheral resistance and renal adaptations that may promote failure of the hypertrophied heart. The aim of the present paper is to discuss the potential role of the renin angiotensin system and its inhibitors in cardiac hypertrophy and failure.