Published Online
on April 26, 2004

A more recent version of this article appeared on June 1, 2004

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Submitted on March 4, 2004
Revised on March 10, 2004

Eplerenone Prevents Salt-Induced Vascular Remodeling and Cardiac Fibrosis in Stroke-Prone Spontaneously Hypertensive Rats

Dierk H. Endemann; Rhian M. Touyz; Marc Iglarz; Carmine Savoia; and Ernesto L. Schiffrin^*

From the CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Canada.

^* To whom correspondence should be addressed. E-mail: ernesto.schiffrin{at}ircm.qc.ca.

Abstract--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.

Key words: rats, stroke-prone SHR • aldosterone • resistance • arteries • remodeling • heart • collagen

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