Implications of local angiotensin production in cardiovascular physiology and pharmacology.

The traditional concept of the renin-angiotensin system is a circulation-borne endocrine system whose components are secreted by different organs, i.e., renin from the kidney, angiotensinogen from the liver and angiotensin-converting enzyme from the lung. The product of the biochemical cascade, angiotensin II, acts on specific receptors on multiple target organs. Recent data, however, demonstrate that renin and angiotensin are synthesized locally in many tissues. The emerging concept--that angiotensin is produced locally at tissue sites by an endogenous renin-angiotensin system--has important implications to our understanding of cardiovascular homeostasis. This 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 as well as local intrarenal events. An important mechanism of action of converting enzyme inhibitors may be the blockade of tissue angiotensin generation. Hence, the tissue distribution and kinetics of converting enzyme inhibitors may be an important determinant of drug action. These findings have led us to speculate that aberrant tissue renin, angiotensinogen gene expression(s) or abnormalities in the regulation of the local renin-angiotensin system may result in such cardiovascular disorders as vasospasm, hypertension and cardiac hypertrophy.