Circulating and tissue angiotensin systems.

Angiotensin has many different actions, most of which relate, either directly or indirectly, to the regulation of blood pressure, fluid, and electrolyte homeostasis (1, 2). In addition to potent vasoconstrictor effects, actions ofangiotensin on vasculature in- clude the stimulation ofprostaglandin release (3), the modulation of angiotensin receptor number (4), and the stimulation of an- giogenesis (5). Angiotensin also has important actions on the central and peripheral nervous systems, the adrenal, kidney, in- testine, and heart (6-1 1). Given these multiple diverse actions of angiotensin, two important questions are (a) which of these actions represent normal physiological events, and (b) whether such actions may assume a pathogenic role. These questions have recently been placed in sharper focus by the clinical ap- plication of inhibitors of the renin-angiotensin system (RAS),' and in particular, the use of converting enzyme inhibitors (CEIs) for the treatment of hypertension. Any attempt to answer these questions requires an accurate concept ofthe RAS. The purpose ofthis review is to discuss new concepts concerning angiotensin production by the circulating RAS, how these relate to angio- tensin production within tissues, and the possible mechanisms by which CEIs lower blood pressure. The study of tissue angio- tensin systems is still at an early stage. In this review I have attempted to synthesize a coherent model of the interaction be- tween the circulating and tissue angiotensin systems, which might assist in the interpretation of new developments in this area.