The role of angiotensin II receptors in vascular regulation.

Plasma-membrane receptors for angiotensin II (AII) have been identified in many AII-responsive tissues involved in the control of blood pressure via direct or indirect actions on vascular contractility. The specific, high-affinity receptors for AII in adrenal zona glomerulosa, vascular smooth muscle, kidney, brain, and anterior pituitary gland exhibit generally similar binding properties. However, the AII receptors in adrenal zona glomerulosa and vascular smooth muscle undergo reciprocal regulatory changes during alterations in sodium intake. These appear to be mediated by changes in circulating AII and are accompanied by parallel changes in sensitivity to AII. The AII receptors in the anterior pituitary gland are located in lactotrophs and corticotrophs and mediate the stimulatory actions of AII upon prolactin and ACTH secretion, acting in conjunction with other hypothalamic regulators. The anterior pituitary receptors are not affected by changes in sodium balance or AII infusion, in contrast to adrenal and vascular AII receptors, but exhibit similar ligand-binding properties to the sites present in other tissues. In the brain, AII receptors are present in several discrete regions and are particularly concentrated in the circumventricular organs. During dehydration, AII receptors are increased in the subfornical organ, but show no significant changes in the other circumventricular organs. The increase in subfornical-organ receptors is analogous to the up-regulation of AII sites in the adrenal cortex during sodium deficiency and may have a potentiating action upon the dipsogenic role of AII during dehydration. Mapping of AII receptors of the brain by topical autoradiography has revealed a highly characteristic pattern of distribution in brain regions concerned with drinking, adrenergic control, blood-pressure regulation, and hypothalamic control of pituitary-hormone secretion. In the rat kidney, AII receptors have been localized in the cortex and medulla by topical autoradiography with 125I-[Sar1]AII. The renal cortical receptors appear to be localized in glomeruli, whereas the AII receptors in the renal medulla are distributed diffusely in medullary tissue and also as localized radiating stripes which correspond to the vasa rectae bundles. The location of the renal receptors for AII in cortical and medullary sites emphasizes the multiplicity of actions of the octapeptide upon the individual compartments of the kidney.