Tissue renin angiotensin systems.

The RAAS is a powerful regulator of vascular tone and intravascular volume and of tissue architecture and a variety of other functions. The recent appreciation of the immunoregulatory role of angiotensin II and its possible involvement in the genesis of atherosclerosis and in plaque rupture all speak to the wide-ranging physiologic and pathophysiologic activities of the peptide. So do its actions in fat cell differentiation and in neuromodulation. The system exists in the circulation, and RAASs, whole or partial, exist in many tissues. These systems are regulated at many levels ranging from the synthesis of renin to the dimerization of angiotensin receptors. Regulation occurs in multiple tissues and, as a result, tissue concentrations of angiotensin II and the concentration of other RAS components and their active metabolites can vary independently of the circulating system in these tissues. An RAS seems also to function within certain cells. Therapeutic interventions involving ACEIs and ARBs seem likely to provide benefit at least in part through the interruption of local systems. It is to be expected that with enhanced understanding of the biology of the multiple RASs, new suggestions for therapeutic interventions will be forthcoming.