Abstract
This study was designed to examine the hypothesis that a calcium channel blocker nifedipine (CCB) could enhance the cardioprotective effect of an angiotensin-II receptor blocker candesartan (ARB) in the treatment for heart failure. Isoproterenol (ISP) was injected into male rats at 300 mg/kg to produce progressive heart failure. Three months later, the rats were divided into 4 groups and treated for 4 weeks with 1) vehicle (n=20), 2) ARB at 0.2 mg/kg/day (n=6), 3) CCB at 10 mg/kg/day (n=6), or 4) both drugs (n=8). Rats injected with saline served as controls (n=13). ISP caused severe myocardial degeneration and decreased the capillary density (Dcap) of the left ventricular (LV) myocardium (mean±SD: 2,197±627 vs. 2,847 ±298 N/mm2 for normal controls), while increasing plasma thiobarbituric acid-reactive substances (TBARS; 3.6±1.1 vs. 1.9±0.5 nmol/ml). Although ARB therapy preserved cardiac morphology, it had little effect on Dcap or oxidative stress. On the other hand, CCB decreased plasma TBARS and 4-hydroxy-2-nonenal protein expression in LV myocardium. Furthermore, the combination of CCB and ARB increased Dcap and preserved the ultrastructure of LV myocardium, so this combination may be a useful option for the treatment of heart failure.
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Okuda, N., Hayashi, T., Mori, T. et al. Nifedipine Enhances the Cardioprotective Effect of an Angiotensin-II Receptor Blocker in an Experimental Animal Model of Heart Failure. Hypertens Res 28, 431–438 (2005). https://doi.org/10.1291/hypres.28.431
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DOI: https://doi.org/10.1291/hypres.28.431
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