Evolving Concepts of the Renin-Angiotensin System

The traditional concept of the renin-angiotensin system (RAS) is a circulation-borne endocrine system, the components of which are secreted by various organs. The product of this biochemical cascade, angiotensin II, acts on specific receptors on multiple target organs. Activation of this circulating system has been shown to result in vasoconstriction and hypertension. In addition to this endocrine system, evidence is emerging that the renin-angiotensin system also exists at multiple local tissue sites. Recent data demonstrating that inhibitors of the RAS are capable of lowering blood pressure in the presence of suppressed as well as elevated plasma renin activity (PRA) have given rise to the hypothesis that these inhibitors exert a large part of their effect on angiotensin that is synthesized by and contained in local tissues. The concept implies that local angiotensin concentrations may exceed those of plasma levels and may play an important role in the tonic control of vascular resistance, cardiac and adrenal functions, and intrarenal events. The hypothesis could explain the broad spectrum of activity of angiotensin-converting enzyme (ACE) inhibitors in hypertensives as well as their continuing antihypertensive activity after plasma ACE levels have been restored.