The cardiac renin-angiotensin system. From basic research to clinical relevance.

Local, tissue-resident renin-angiotensin systems are increasingly being recognized as important neurohumoral regulatory units which may act independently of the circulating system. Here, the evidence supporting the existence, functional integration, and physio-pathological role of the cardiac renin-angiotensin system is reviewed. The elements of the catalytic cascade of the system, renin, angiotensinogen, angiotensin-converting enzyme, and the specific angiotensin receptor have all been identified in cardiac tissues as synthesized there by local expression of the respective genes. Modulation of gene expression in response to various perturbations has been demonstrated, and may be regulated 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 a functionally integrated catalytic pathway for the production of angiotensin II. Through its specific receptors angiotensin mediates profound effects on cardiomyocyte function and, as we are beginning to learn, on structure and growth. The remarkable therapeutic potential of drugs that inhibit the renin-angiotensin system in a number of cardiovascular disorders emphasizes the likely role that the cardiac RAS plays in health and disease. Continued efforts at elucidating the precise nature of this role will not only enhance our understanding of this system, but also translate into further clinical progress.