Interactions of high salt intake and the response of the cardiovascular system to aldosterone.
High salt intake contributes to the risk of hypertension, and this effect is in part mediated by the physiologic action of aldosterone on renal mineralocorticoid receptors. However, the actions of aldosterone are not restricted to the kidneys, because aldosterone can bind to mineralocorticoid receptors in the heart, vasculature, and brain to produce structural and functional changes that lead to target organ damage. Experimental and clinical studies show that, in the setting of high salt intake, blocking aldosterone at the mineralocorticoid receptor reduces progression to target organ damage and preserves vascular function. In many cases, these benefits are independent of changes in blood pressure. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have short-term effects on reducing aldosterone levels, but frequently aldosterone levels return to pretreatment levels during long-term therapy. Aldosterone blockade may be more completely achieved with mineralocorticoid receptor antagonists. Spironolactone has been shown to have substantial and significant benefits in experimental and clinical studies of cardiac dysfunction. Eplerenone is a selective aldosterone blocker with a greater binding affinity for mineralocorticoid receptors than for androgen and progesterone receptors. Eplerenone has similarly demonstrated significant benefits in experimental animals and in patients with left ventricular dysfunction after myocardial infarction. Thus, aldosterone blockade with mineralocorticoid receptor antagonists offers target organ protection and may blunt some of the adverse effects of chronic high salt intake.
Conlin
Paul R
PR
Division of Endocrinology, Diabetes and Hypertension Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. pconlin@partners.org
D000450:Aldosterone / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000517:prevention & control; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D018161:Receptors, Mineralocorticoid / Q000187:drug effects* / Q000378:metabolism; D018570:Risk Assessment; D012982:Sodium, Dietary / Q000009:adverse effects*
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D012982:Sodium, Dietary; D000450:Aldosterone