Early Spironolactone Treatment Attenuates Heart Failure Development by Improving Myocardial Function and Reducing Fibrosis in Spontaneously Hypertensive Rats.
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BACKGROUND: We evaluated the role of the aldosterone blocker spironolactone in attenuating long-term pressure overload-induced cardiac remodeling and heart failure (HF) in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: Thirteen month-old male SHR were assigned to control (SHR-C, n=20) or spironolactone (SHR-SPR, 20 mg/kg/day, n=24) groups for six months. Normotensive Wistar-Kyoto rats (WKY, n=15) were used as controls. Systolic blood pressure was higher in SHR groups and unchanged by spironolactone. Right ventricular hypertrophy, which characterizes HF in SHR, was less frequent in SHR-SPR than SHR-C. Echocardiographic parameters did not differ between SHR groups. Myocardial function was improved in SHR-SPR compared to SHR-C [developed tension: WKY 4.850.68; SHR-C 5.221.64; SHR-SPR 6.801.49 g/mm2; -dT/dt: WKY 18.0 (16.019.0); SHR-C 20.8 (18.425.1); SHR-SPR 28.9 (24.234.6) g/mm2/s]. Cardiomyocyte cross-sectional area and total collagen concentration (WKY 1.060.34; SHR-C 1.850.63; SHR-SPR 1.280.39 g/mg wet tissue) were greater in SHR-C than WKY and SHR-SPR. Type 3 collagen expression was lower in SHR-C than WKY and unchanged by spironolactone. Soluble collagen, type I collagen, and lysyl oxidase did not differ between groups. CONCLUSION: Early spironolactone treatment decreases heart failure development frequency by improving myocardial systolic and diastolic function and attenuating hypertrophy and fibrosis in spontaneously hypertensive rats.
