Eplerenone Prevents Salt-Induced Vascular Remodeling and Cardiac Fibrosis in Stroke-Prone Spontaneously Hypertensive Rats
作者:
Dierk Endemann,
Rhian Touyz,
Marc Iglarz,
Carmine Savoia,
Ernesto Schiffrin,
期刊:
Hypertension: Journal of The American Heart Association
(OVID Available online 2004)
卷期:
Volume 43,
issue 6
页码: 1252-1257
ISSN:0194-911X
年代: 2004
出版商: OVID
关键词: rats;stroke-prone SHR;aldosterone;resistance;arteries;remodeling;heart;collagen
数据来源: OVID
摘要:
We examined the effect of different levels of salt intake on the role of aldosterone on cardiac and vascular changes in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Eleven-week-old SHRSP were fed high-salt (4.2% NaCl), normal-salt (0.28%), or low-salt (0.03%) diets with or without eplerenone (100 mg/kg per day, in food) for 5 weeks. A group of high-salt SHRSP was also treated with hydralazine (25 mg/kg per day). Blood pressure increased more in high-salt rats than in other groups (P< 0.001). Eplerenone prevented further blood pressure rise in salt-loaded rats, with little effect on control and low-salt SHRSP. Increased media-to-lumen ratio of mesenteric resistance arteries induced by salt (P< 0.01) was prevented by eplerenone (P< 0.01). Maximal acetylcholine-induced vasodilation was impaired under salt loading (P< 0.01), but improved under eplerenone (P< 0.01). Eplerenone prevented (P< 0.01) increased heart weight and left and right ventricular collagen deposition induced by high salt. Blood pressure lowering by hydralazine in high-salt SHRSP did not influence endothelial function or left ventricular collagen. Our study demonstrates salt-dependency of aldosterone effects on severity of hypertension, endothelial dysfunction, and cardiac and vascular remodeling in SHRSP. These effects were attenuated by eplerenone, particularly in the salt-loaded state, underlining the pathophysiological role of aldosterone in salt-sensitive hypertension.
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