Protective effect of diltiazem on myocardial ischemic rats induced by isoproterenol

Abstract

The aim of the present study was to analyze the effect of diltiazem on myocardial fibrosis and remodeling of connexin43 (Cx43) in myocardial ischemic rats and mechanisms underlying these processes. A total of 36 Sprague-Dawley rats were ra ndom ly allo cated into three groups (control, isoproterenol and isoproterenol with diltiazem). The myocardial ischemic model was established by 5 mg/kg/day isoproterenol administration for 7 days, and the diltiazem group received 25 mg/kg/day diltiazem for 4 weeks. Following the treatment, paraffin sections were prepared to observe microstructural changes and to evaluate the concentration of Ca2+ in myocardium. The expression of transforming growth factors-β1 (TGF-β1), mothers against decapentaplegic homologues (Smad)2 and 7 and Cx43, were a na lyze d by rever se transcription-quantit ative polymerase chain reaction and western blotting. The percentage Cx43 expression in intercalated disks was evaluated using immunohistochemistry. Fibrosis did not differ significantly between the control and the diltiazem-treated group. The concentration of Ca2+ increased in the myocardium of model rats. The expression of Smad7 and Cx43 was decreased in the rat model, while the expression of TGF-β1 and Smad2 was increased. There was a significant decrease in the relative abundance of intercalated disk Cx43 in the model group. The results of the present study suggest that diltiazem may serve a protective role during remodeling of myocardial ischemia, especially in fibrosis and Cx43 remodeling.