Central hypertensive effects of aldosterone.
The soluble mineralocorticoid receptor bound to an agonist acts as a transcription factor for several genes relevant to ion transport by kidney and colon epithelial cells and is a major regulator of electrolyte and fluid homeostasis. Mineralocorticoids, the most prominent of which is aldosterone, also influence the activity of nonepithelial target cells, including vascular smooth muscle cells, by altering intracellular ion transport and content. Evidence is summarized for mineralocorticoid modulation of neuronal activity in a center or centers within the brain, probably in the periventricular area of the anterior hypothalamus, where information on electrolyte, fluid, and cardiovascular status is received and integrated, resulting in alterations in central sympathetic efferent activity. These functions are distinct from central aldosterone effects on salt appetite and peripheral trophic effects on cardiovascular tissue. The isolated mineralocorticoid receptor binds several adrenal steroids, including aldosterone and the major glucocorticoids, with equal affinity. Ligand specificity for the mineralocorticoid receptor differs between tissues, including different organs in the brain. Specificity is conferred extrinsically by the 11-beta-hydroxysteroid dehydrogenase enzymes in transport epithelia, but mechanisms for mineralocorticoid ligand specificity have not been completely defined in the brain. The functional interaction between the mineralocorticoid receptor bound to different ligands and between the mineralocorticoid and glucocorticoid receptors is complex and as yet unresolved. Evidence is presented for the de novo synthesis of adrenal corticosteroids in the brain which may, by paracrine regulation of central control mechanisms, be relevant for certain clinical and experimental forms of hypertension characterized by low circulating levels of mineralocorticoids which respond to mineralocorticoid receptor antagonists.
Gómez-Sánchez
E P
EP
Department of Internal Medicine, University of Missouri-Columbia, USA. intmdepg@showme.missouri.edu
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid / Q000819:agonists
D000305:Adrenal Cortex Hormones; D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone