Why the study?
Does spironolactone alone or in combination with enalapril or verapamil improve cardiac structure in spontaneously hypertensive rats?
Does spironolactone alone or in combination with enalapril or verapamil improve cardiac structure in spontaneously hypertensive rats?
In a rat model of hypertension, combining spironolactone with enalapril or verapamil is more effective than spironolactone monotherapy at preventing myocardial structural alterations.
Combination therapy merits further preclinical testing in hypertension; leaves open clinical translation of spironolactone monotherapy.
The present study aims to objectivate by laser scanning confocal microscopy, the cardiac structure of the spontaneously hypertensive rats (SHR) treated with different doses of spironolactone, either alone or in combination with an angiotensin converting enzyme inhibitor or with a calcium channel blocker. Thirty SHRs were divided into six groups and treated during 13 weeks as follows: control, spironolactone (5, 10 and 30 mg/kg/day), spironolactone + enalapril and spironolactone + verapamil. Spironolactone action on the SHR blood pressure (BP) was dose-dependent. The cardiac hypertrophy was affected by the treatment with spironolactone (high dose) or a combination of spironolactone and Enalapril. The myocardial structure was less affected by the spironolactone monotherapy (at all doses) showing hypertrophied cardiac myocytes, focal areas of the reactive fibrosis, inflammatory infiltrate. The treatment with spironolactone in combination with enalapril or verapamil prevented these alterations. In conclusion, the monotherapy with spironolactone had only a limited effect in the preservation of the myocardial structure and in the attenuation of the interstitial fibrosis in SHRs, even after high dose. This action on the myocardium is more efficient when the spironolactone (even in medium dose) was associated with enalapril or verapamil.
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Pereira et al. (2002) studied this question.
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