title: Mineralocorticoid receptors and hypertension.
abstract: Mineralocorticoid receptors (MR) have equal affinity for the mineralocorticoid aldosterone, and the physiological glucocorticoids cortisol and corticosterone. In epithelial tissues in vivo, MR are protected against glucocorticoid occupancy by the enzyme 11 beta-hydroxysteroid dehydrogenase, allowing access by the lower circulating levels of the physiological mineralocorticoid aldosterone. In non-epithelial tissues, including the heart and most areas of the central nervous system, MR are not so protected, and their physiological ligand is cortisol/corticosterone. Intracerebroventricular infusion studies have shown that aldosterone occupancy of such unprotected circumventricular MR is necessary for mineralocorticoid hypertension, and the hypertensinogenic effects of peripherally infused aldosterone can be blocked by intracerebroventricular infusion of the MR antagonist RU28318. Prolonged (8 weeks) administration of mineralocorticoids to salt-loaded rats has been shown to be followed by hypertension, cardiac hypertrophy and cardiac fibrosis. Whether the hypertrophy and fibrosis reflect primary effects of aldosterone via cardiac MR, or effects secondary to occupancy of protected, epithelial MR, remains to be determined, as does the mechanism of action of salt loading in this model of mineralocorticoid hypertension.
authors.affiliation: Baker Medical Research Instiute, Prahan, Victoria, Australia.
authors.forename: J W
authors.initials: JW
authors.lastname: Funder
mesh_terms: D000450:Aldosterone / Q000502:physiology; D000818:Animals; D004848:Epithelium / Q000502:physiology; D006331:Heart Diseases / Q000150:complications; D006973:Hypertension / Q000503:physiopathology*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D012965:Sodium Chloride / Q000378:metabolism
chemical_list: D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D012965:Sodium Chloride; D000450:Aldosterone