Published Online
on November 4, 2002

A more recent version of this article appeared on November 26, 2002

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Submitted on July 26, 2002
Accepted on August 21, 2002

Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt-Treated Rats. Effects of Eplerenone

Patrick Lacolley MD, PhD, Carlos Labat , Alex Pujol , Claude Delcayre PhD, Athanase Benetos MD, PhD, and Michel Safar MD^*

From INSERM EMI U0107 (P.L., C.L., A.P.), INSERM U572 (C.D.), and Department of Internal Medicine, Broussais Hospital (A.B., M.S.), Paris, France.

^* To whom correspondence should be addressed. E-mail: michel.safar{at}brs.ap-hop-paris.fr.

Background—Previous studies have demonstrated the development of cardiac fibrosis in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on in vivo mechanical properties of the carotid artery using echo-tracking system.

Methods and Results—Aldo was administered (1 µg/h) in uninephrectomized Sprague-Dawley rats (SD) receiving a high-salt diet from 8 to 12 weeks of age. Uninephrectomized control SD rats received a normal salt diet without Aldo. Three groups of Aldo-salt rats were treated with 1, 10, or 30 mg/kg^-1 · d^-1 of Epl by gavage. Elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The structure of the arterial wall was analyzed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo produced increased systolic arterial pressure, pulse pressure, Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities compared with controls without Aldo. No differences in collagen mRNA levels were detected between groups. Epl blunted the increase in pulse pressure in Aldo rats and normalized Einc-wall stress curves, MCSA, and EIIIA Fn. These effects were dose dependent and not accompanied by a reduction in wall stress.

Conclusions—Aldo is able to increase arterial stiffness associated with Fn accumulation, independently of wall stress. The preventive effects of Epl suggest a direct role for mineralocorticoid receptors in mechanical and structural alterations of large vessels in rat hyperaldosteronism.

Key words: arteries • hypertension • elasticity • pharmacology

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