Nipradilol, a new beta-adrenergic blocker, reduces left ventricular remodeling following myocardial infarction in spontaneously hypertensive rats

Abstract

Left ventricular (LV) cavity dilation (remodeling) following myocardial infarction (MI) is a risk factor for morbidity and mortality. This study was undertaken to determine whether nipradilol, a new beta-adrenergic blocker with vasodilating action, reduces LV remodeling after MI produced by coronary ligation in spontaneously hypertensive rats. The effects on LV remodeling of the following drugs, which were administered orally for 4 weeks, were evaluated by assessing LV end-diastolic volume index (LVEDVI): (1) vehicle, (2) nipradilol, 10 mg/kg per day. (3) propranolol, 50 mg/kg per day, and (4) captopril, 30 mg/kg per day. Since LVEDVI depends on infarct size, the effects of the drugs on LVEDVI were compared between rats with a similar infarct size, i.e., moderate, 20%-40%; and large, 40%-60%, on the basis of the histological determination of infarct size. The nipradilol-treated and captopril-treated rats had significantly smaller LVEDVI than did the vehicle-treated rats with both moderate and large infarction (large infarct: 2.48 +/- 0.12 ml/kg for the vehicle group, 1.69 +/- 0.10 ml/kg for the nipradilol group, P < 0.01, and 1.79 +/- 0.14 ml/kg for the captopril group, P < 0.01). In contrast, LVEDVI-in the propranolol-treated rats was significantly greater than that in the vehicle-treated rats with a moderate infarct (2.09 +/- 0.09 ml/kg for the vehicle group versus 2.44 +/- 0.10 ml/kg for the propranolol group, P < 0.05). The results indicate that nipradilol and captopril reduce LV remodeling after MI, whereas propranolol promotes it.