INFLUENCE OF NIFEDIPINE, VERAPAMIL AND DILTIAZEM ON PULMONARY VASCULAR-RESISTANCE AND VASOCONSTRICTORS IN CATS

In the present study, the effects of three classes of L-type calcium c hannel-blocking agents, nifedipine, verapamil and diltiazem, on the lo bar arterial pressure and the vasoconstrictor responses in the pulmona ry vascular bed were compared to those of cromakalim, a K-ATP channel activator, in the anaesthetized cat under controlled pulmonary blood f low and constant left atrial pressure. These drugs were infused intral obarly in doses selected which did not raise left atrial pressure, cha nge cardiac output or alter systemic arterial pressure. Intralobar bol us injections of calcium channel-blocking agents and of the K+ channel activator decreased the lobar arterial pressure in a dose-related man ner when pulmonary vasomotor tone was actively elevated by intralobar arterial infusion of U46619. The pulmonary vasodilator response to the se agents was accompanied by a dose-related decrease of systemic arter ial pressure. In decreasing lobar arterial pressure at elevated pulmon ary vasomotor tone, the order of potency was nifedipine > verapamil > diltiazem, whereas in reducing systemic arterial pressure, the order o f potency was nifedipine > diltiazem > verapamil. The calcium channel- blocking agents were less active than the reference drug, cromakalim, in both vascular beds. Intralobar arterial infusions of nifedipine, ve rapamil and diltiazem, at the rates of 0.03 mu mol/min, 0.2 mu mol/min and 0.1 mu mol/min, respectively, caused no changes in cardiac output and in systemic and pulmonary arterial pressure. Infusion of all thre e calcium-channel-blocking agents blocked the pulmonary vasoconstricto r responses to BAY K 8644 (calcium entry promoter) and U46619 (thrombo xane A(2) mimic). Nifedipine infusion also reduced the pulmonary vasoc onstrictor responses to methoxamine and BHT933 (alpha(1)- and alpha(2) -adrenoceptor agonists, respectively), whereas verapamil infusion redu ced the responses only to methoxamine. Infusion of diltiazem caused no significant decrease of responses to either alpha-adrenoceptor agonis t. The results of the present study suggest that the dihydropyridine, nifedipine, is more potent than the non-dihydropyridines, verapamil an d diltiazem, in reducing the pulmonary vascular resistance and more ef fective in inhibiting the vasoconstrictor responses to the alpha-adren oceptor agonists, to U46619 and to BAY K8644 in the feline pulmonary c irculation at the infusion rates which cause no or little hemodynamic changes.