Localization and function of angiotensin AT 1 receptors

Abstract

The distributions of angiotensin AT 1 and AT 2 receptors have been mapped by in vitro autoradiography throughout most tissues of many mammals, including humans. In addition to confirming that AT 1 receptors occur in sites known to be targets for the physiologic actions of angiotensin, such as the adrenal cortex and medulla, renal glomeruli and proximal tubules, vascular and cardiac muscle and brain circumventricular organs, many new sites of action have been demonstrated. In the kidney, AT 1 receptors occur in high density in renal medullary interstitial cells. The function of these cells, which span the interstitial space between the tubules and the vasa rectae, remains to be determined. Renal medullary interstitial cells possess receptors for a number of vasoactive hormones in addition to AT 1 receptors and this, in concert with their anatomic location, suggests they may be important for the regulation of fluid reabsorption or renal medullary blood flow. In the heart, the highest densities of AT 1 receptors occur in association with the conduction system and vagal ganglia. In the central nervous system, high AT 1 receptor densities occur in many regions behind the blood–brain barrier, supporting a role for neurally derived angiotensin as a neuromodulator. The physiologic role of angiotensin in many of these brain sites remains to be determined. The AT 2 receptor also has a characteristic distribution in several tissues including the adrenal gland, heart, and brain. The role of this receptor in physiology is being elucidated, but it appears to inhibit proliferation and to participate in development. Thus, receptor-binding studies, localizing the distribution of AT 1 and AT 2 receptors, provide many insights into novel physiologic roles of angiotensin.