The cardiac renin-angiotensin system: a synopsis of current experimental and clinical data

Local tissue-resident renin-angiotensin systems are increasingly being recognized as important neurohumoral mediators which may act in concert with, but also independently of the circulating system. Here we review the evidence supporting the existence, functional integration, and physiopathological role of a cardiac renin-angiotensin system which has recently been defined. The elements of the catalytic cascade of the system, renin, angiotensinogen, and angiotensin-converting enzyme have all been demonstrated in cardiac tissues, both on the protein-level and with regard to local expression of the respective genes. Modulation of gene expression in response to various perturbations has been demonstrated, and may occur independently of the plasma or other tissue renin-angiotensin systems. In isolated hearts, generation of the biologically active peptides, angiotensin I and II, has been documented, establishing the capability of this system to act as an independently regulated, functionally integrated catalytic pathway for the production of angiotensin II. Through specific receptors, present in the heart as in other tissues, angiotensin mediates profound effects on cardiomyocyte function and, as we are beginning to learn, on structure and growth. Furthermore, indirect evidence based on specific, beneficial effects of angiotensin converting enzyme inhibiting drugs which are distinct from those of other vasodilators, points to the potential role which this local system may play for physiological function of the heart as well as in a number of pathological derangements of the cardiovascular system.