title: Mineralocorticoid actions in the brain and hypertension.
abstract: Mineralocorticoid receptors (MR) and epithelial sodium channels (ENaC) in the brain mediate central aldosterone-induced sympathetic hyperactivity and hypertension. Enzymes for biosynthesis of aldosterone are present in the brain, and aldosterone can be produced locally in the brain. Hypothalamic aldosterone levels increase in Dahl salt-sensitive rats on high-salt diet, and in Wistar rats with chronic central infusion of sodium-rich artificial cerebrospinal fluid (CSF) or with subcutaneous infusion of angiotensin II. Functional studies using antagonists of MR, ENaC, and ouabain-like compounds ("ouabain"), as well as specific aldosterone synthase inhibitors, suggest that an increase in local synthesis of aldosterone via MR and ENaC in the brain increases "ouabain" and thereby causes enhanced AT(1) receptor stimulation, leading to sympathoexcitation and hypertension. An increase in CSF sodium or an increase in angiotensinergic output from circumventricular organs such as the subfornical organ projecting to hypothalamic nuclei may increase local production of aldosterone and "ouabain" in magnocellular neurons in the supraoptic nucleus and paraventricular nucleus. This aldosterone-"ouabain" neuromodulatory mechanism appears to play a major role in salt-induced or angiotensin II-induced hypertension.
authors.affiliation: Hypertension Unit, University of Ottawa Heart Institute, H3238, 40 Ruskin Street, Ottawa, ON K1Y 4W7, Canada. bhuang@ottawaheart.ca
authors.forename: Bing S
authors.initials: BS
authors.lastname: Huang
authors.forename: Frans H H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II; D001921:Brain / Q000503:physiopathology*; D002555:Cerebrospinal Fluid; D019405:Cytochrome P-450 CYP11B2; D053503:Epithelial Sodium Channels; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008901:Mineralocorticoids; D010042:Ouabain; D011311:Pressoreceptors; D012084:Renin-Angiotensin System
chemical_list: D000305:Adrenal Cortex Hormones; D053503:Epithelial Sodium Channels; D008901:Mineralocorticoids; D000804:Angiotensin II; D000450:Aldosterone; D010042:Ouabain; D019405:Cytochrome P-450 CYP11B2