ROLE OF ANGIOTENSIN IN THE EXTRAVASCULAR SYSTEM

Angiotensin receptors are present in many tissue types, including adre nal cortex, renal glomeruli, heart, hypothalamus, liver, pancreas, pit uitary, platelets, renal tubules, uterus and vascular smooth muscle. T wo high-affinity receptor subtypes have been identified by radioligand binding with antagonists: losartan (DuP 753/MK954) identifies AT1 rec eptors; PD123177 and CGP42112A are markers for AT2 receptors. Angioten sin II may be produced locally in tissues outside the humoral system. For example, it is found in the brain, kidney and heart. Within the br ain, the heptapeptide angiotensin(1-7) mimics some effects of angioten sin II, but may be formed directly from angiotensin I. Evidence for no n-ACE-mediated angiotensin II production has been reported in the hear t. Intravascular angiotensin II receptors are implicated in the centra l release of vasopressin and other hypophyseal hormones, in increasing sympathetic outflow, in the thirst response and, possibly, in cogniti ve function; in the inotropic and chronotropic effects of angiotensin II on the heart as well as in growth/hypertrophy; in the control of al dosterone release and in the balance between cortisol and aldosterone secretion; and in modulating sodium, chloride and bicarbonate transpor t within the kidney. Effects on the reproductive system, liver and pan creas have not been established. The pharmacological effects of angiot ensin II antagonists will depend on their distribution characteristics as well as affinity for specific receptor subtypes. At present, howev er, the physiological role of AT2 receptors has not been defined.