Tissue renin-angiotensin systems: focus on the heart

Recent findings support the existence of independently functioning, local renin-angiotensin systems in a number of tissues. The clinical importance that inhibitors of the renin-angiotensin system have gained in the treatment of hypertension and cardiac failure, as well as molecular biology data, suggest that a functional, tissue renin-angiotensin system is present in the heart. Using several experimental approaches we present evidence to support the existence and the possible physiopathological relevance of such a cardiac renin-angiotensin system. Tissue angiotensins were documented and quantified in different regions of the heart by high performance liquid chromatography combined with specific radio-immunoassay. Reduction of cardiac angiotensin after administration of converting enzyme inhibitors in nephrectomized animals indicates that these peptides are generated locally. Effects of converting enzyme inhibitors on angiotensin II-dependent facilitation of cardiac sympathetic tone further support this concept and emphasize the potential physiological role of a cardiac renin-angiotensin system. Further, direct evidence for local generation of angiotensin II in the myocardium is provided by assessment of the intracardiac conversion of angiotensin I to angiotensin II and by measurement of the activity of angiotensin converting enzyme in the heart.