Published online before print November 4, 2002, doi: 10.1161/01.CIR.0000039328.33137.6C
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(Circulation. 2002;106:2848.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt–Treated Rats
Effects of Eplerenone
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.
Correspondence to Pr Michel Safar, Médecine Interne 1 Hôpital Broussais, 96 rue Didot 75674, Paris, Cedex 14, France. 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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