Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extra-adrenal sodium-retaining factor was first described in Circulation Research in 1964. This factor increases the responsiveness of the renal tubules to aldosterone in heart failure, and marked sodium retention occurs with resultant edema or ascites. Evidence for the extra-adrenal sodium-retaining factor is presented in two models of experimental heart failure in dogs and in dogs with thoracic caval constriction and a low cardiac output. Since the nature of this sodium-retaining factor remains unknown, several of the recently discovered factors that influence kidney function and that might alter the responsiveness of the renal tubules to a mineralocorticoid are described. These factors include atrial natriuretic peptide, nitric oxide, 11 beta-hydroxysteroid dehydrogenase activity, the endothelins, and the intrarenal tissue renin-angiotensin system. It is suggested that the nature and action of the sodium-retaining factor be reinvestigated in lieu of the new knowledge of kidney function. The applicability of newly developed experimental models of heart failure for study of the extra-adrenal factor is discussed; these include coronary artery ligation in rats, cardiac pacing in the dog, and application of transmyocardial direct current shock to local myocardial areas in dogs.
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PMID:An extra-adrenal sodium-retaining factor in congestive heart failure. 942 Jun 48

Chronic elevation of plasma aldosterone contributes to heart failure. Mineralocorticoid receptor (MR) antagonism is cardioprotective in such a setting, but whether such protection occurs in the presence of low-aldosterone concentrations remains unclear. We investigated whether MR blockade attenuates cardiac hypertrophy and failure in rats with salt-sensitive hypertension. Dahl salt-sensitive (DS) rats fed a high-salt diet from 7 weeks develop concentric left ventricular (LV) hypertrophy secondary to hypertension at 12 weeks followed by heart failure at 19 weeks (DS-CHF). DS rats on such a diet were treated with a non-antihypertensive dose of the selective MR antagonist eplerenone from 12 to 19 weeks. Renin activity and aldosterone concentration in plasma were decreased in DS-CHF rats compared with controls. LV hypertrophy and fibrosis, as well as macrophage infiltration around coronary vessels, were apparent in DS-CHF rats. The amounts of mRNAs for 11beta-hydroxysteroid dehydrogenase type 1, MR, monocyte chemoattractant protein 1, and osteopontin were increased in these hearts. Treatment of DS-CHF rats with eplerenone inhibited these changes in gene expression, as well as coronary vascular inflammation and heart failure. Eplerenone attenuated both the decrease in the ratio of reduced to oxidized glutathione and the increase in NADPH oxidase activity apparent in DS-CHF rat hearts. MR blockade with eplerenone thus resulted in attenuation of LV hypertrophy and failure, without an antihypertensive effect, in rats with low-aldosterone hypertension. The beneficial cardiac effects of eplerenone are likely attributable, at least in part, to attenuation of myocardial oxidative stress and coronary vascular inflammation induced by glucocorticoid-activated MRs.
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PMID:Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and failure in low-aldosterone hypertensive rats. 1650 9