Mineralocorticoids, salt and high blood pressure.
Essential hypertensive patients often respond to treatments mitigating mineralocorticoid action, even though circulating levels of these steroids are within normal ranges. In addition to the kidney, mineralocorticoid or Type I receptors are found in the brain and vascular smooth muscle where they mediate effects associated with several forms of experimental hypertension. Studies in which discrete anatomic or functional areas of the brain have been ablated demonstrate that the periventricular areas of the hypothalamus and the central sympathetic and baroreceptor systems are crucial for the development of hypertension in the renoprival, DOCA salt, and Dahl salt-sensitive rat. Intracerebroventricular (i.c.v.) infusion of aldosterone in both rats and dogs at doses that do not raise serum levels above normal produce hypertension. The hypertension produced by systemic mineralocorticoid excess, adrenal regeneration, and i.c.v. or oral administration of glycyrrhetinic acid or carbenoxolone in genetically normotensive rats and by dietary salt in the Dahl salt-sensitive rat is inhibited by the i.c.v. infusion of a mineralocorticoid receptor antagonist or a Na+ channel-selective amiloride analog. Recent data demonstrate the extraadrenal synthesis of steroids in aortic endothelial cells, smooth muscle cells and the brain. The role of the extraadrenal synthesis of steroids raises new avenues for research into the causes of hypertension.
Gómez-Sánchez
E P
EP
Department of Internal Medicine, University of Missouri-Columbia, USA.
Zhou
M
M
Gomez-Sanchez
C E
CE
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D000311:Adrenal Glands / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D004285:Dogs; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D008901:Mineralocorticoids / Q000378:metabolism / Q000494:pharmacology*; D009154:Mutation; D051381:Rats; D011919:Rats, Inbred Strains; D012038:Regeneration / Q000187:drug effects*; D012492:Salts / Q000378:metabolism / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics
D000305:Adrenal Cortex Hormones; D008901:Mineralocorticoids; D012492:Salts; D013252:Steroid 11-beta-Hydroxylase