CENTRAL HYPERTENSIVE EFFECTS OF ALDOSTERONE

The soluble mineralocorticoid receptor bound to an agonist acts as a t ranscription factor for several genes relevant to ion transport by kid ney and colon epithelial cells and is a major regulator of electrolyte and fluid homeostasis. Mineralocorticoids, the most prominent of whic h is aldosterone, also influence the activity of nonepithelial target cells, including vascular smooth muscle cells, by altering intracellul ar ion transport and content. Evidence is summarized for mineralocorti coid modulation of neuronal activity in a center or centers within the brain, probably in the periventricular area of the anterior hypothala mus, where information on electrolyte, fluid, and cardiovascular statu s is received and integrated, resulting in alterations in central symp athetic efferent activity. These functions are distinct from central a ldosterone effects on salt appetite and peripheral trophic effects on cardiovascular tissue. The isolated mineralocorticoid receptor binds s everal adrenal steroids, including aldosterone and the major glucocort icoids, with equal affinity. Ligand specificity for the mineralocortic oid receptor differs between tissues, including different organs in th e brain. Specificity is conferred extrinsically by the 11-beta-hydroxy steroid dehydrogenase enzymes in transport epithelia, but mechanisms f or mineralocorticoid ligand specificity have not been completely defin ed in the brain. The functional interaction between the mineralocortic oid receptor bound to different ligands and between the mineralocortic oid and glucocorticoid receptors is complex and as yet unresolved. Evi dence is presented for the de novo synthesis of adrenal corticosteroid s in the brain which may, by paracrine regulation of central control m echanisms, be relevant for certain clinical and experimental forms of hypertension characterized by low circulating levels of mineralocortic oids which respond to mineralocorticoid receptor antagonists. (C) 1997 Academic Press.