THE RENIN-ANGIOTENSIN SYSTEM AS A TARGET FOR THERAPEUTIC INTERVENTION

Experimental studies have identified local renin-angiotensin systems in a variety of tissues. The importance of these systems is indicated by the evidence that, in genetic models of hypertension in the rat, blood pressure is elevated by the renin gene independently of changes in plasma levels of renin. Trials of angiotensin-converting enzyme (ACE) inhibitors in human left ventricular dysfunction indicate that they improve the mortality from myocardial infarction (MI); high plasma renin activity is associated with increased risk for myocardial infarction (MI), and an ACE gene allele increases the risk for death from MI. These data point to the importance of the renin-angiotensin system in both ischemic heart disease and hypertension, even without increased circulating levels of plasma renin. The degree to which ACE inhibitors are beneficial as a result of hemodynamic actions on the heart and coronary tree and the extent to which they affect local tissue systems independently of their hemodynamic effect still remains to be clarified.