Cardiovascular actions of the calmodulin inhibitor felodipine

The cardiovascular effects of intravenous (1.5-10 nmol X kg-1) and intracoronary (50 nmol) administration of felodipine, 4-(2,3-dichlorophenyl)-1,4-dihydro-2, 6-dimethyl-3-ethoxycarbonyl-5-methoxycarbonylpyridine, were studied in anaesthetized pigs. Following intravenous administration dose-dependent decreases were observed in left ventricular systolic blood pressure (up to 30%) and in the resistances of the systemic (up to 40%) and coronary vascular beds (up to 45%), whereas heart rate, cardiac output, myocardial contractility (regional and global), and left ventricular end-diastolic pressure were minimally affected. Myocardial blood flow increased independently of the dose (20%), while the coronary venous O2-content more than doubled. The concomitant decrease in myocardial O2-consumption (up to 30%) was dose-dependent in the range from 1.5-6.75 nmol X kg-1. Intracoronary administration of 50 nmol had only minor effects on global and regional myocardial performance but produced a doubling of the coronary blood flow which was accompanied by a 70% decrease in myocardial O2-extraction. O2-consumption decreased considerably more (35%) than after intravenous administration in spite of the minimal decrease in O2-demand (7%). We conclude that felodipine dilates both systemic and coronary blood vessels. Although the reduction in myocardial O2-consumption is primarily caused by the reduction in afterload, a direct effect on myocardial metabolism can also be involved.