Addition of spironolactone to an angiotensin-converting enzyme inhibitor decreases lung congestion and edema in Dahl hypertensive rats

Abstract

We investigated the effect of adding spironolactone to treatment with an angiotensin-converting enzyme (ACE) inhibitor, imidapril, in Dahl salt-sensitive (DS) hypertensive heart failure rats with preserved systolic function. Male DS rats were fed laboratory chow containing 8% NaCl from 7 weeks of age. Rats were divided into four groups and treated for 9 weeks with vehicle alone (water; n = 23), the ACE inhibitor imidapril (1 mg kg⁻¹ day⁻¹; n = 16), spironolactone (2 mg kg⁻¹ day⁻¹; n = 15), or a combination of imidapril and spironolactone at the doses above (n = 16). The left ventricular weight to body weight (BW) ratio was significantly lower in the imidapril group (3.28 ± 0.30 mg g⁻¹) and the combination group (3.34 ± 0.38 mg g⁻¹) than in the vehicle group (3.71 ± 0.46 mg g⁻¹). Adding spironolactone to imidapril inhibited an increase in the ratio of lung weight to BW (4.38 ± 0.50 mg g⁻¹) related to high salt intake, while monotherapy (imidapril group, 4.61 ± 0.90 mg g⁻¹; spironolactone group, 5.40 ± 2.50) did not significantly change the ratio from that seen with vehicle treatment (6.32 ± 3.62 mg g⁻¹). All active treatments (imidapril, 0.66% ± 0.67%; spironolactone, 0.51% ± 0.55%; both together, 0.31% ± 0.26%) inhibited a salt-intake related increase in the percentage area representing fibrous tissue compared with vehicle treatment alone (1.81% ± 1.51%). These findings suggest that adding spironolactone to an ACE inhibitor is more effective in improving pulmonary congestion and edema in hypertensive heart failure with preserved systolic function than an ACE inhibitor alone.