ARCHIVES INTERNATIONALES DE PHARMACODYNAMIE ET DE THERAPIE, cilt.328, ss.165-179, 1994 (SCI İndekslerine Giren Dergi)
In the present study, the effects of three classes of L-type calcium channel-blocking agents, nifedipine, verapamil and diltiazem, on the lobar arterial pressure and the vasoconstrictor responses in the pulmonary vascular bed were compared to those of cromakalim, a K-ATP channel activator, in the anaesthetized cat under controlled pulmonary blood flow and constant left atrial pressure. These drugs were infused intralobarly in doses selected which did not raise left atrial pressure, change cardiac output or alter systemic arterial pressure. Intralobar bolus injections of calcium channel-blocking agents and of the K+ channel activator decreased the lobar arterial pressure in a dose-related manner when pulmonary vasomotor tone was actively elevated by intralobar arterial infusion of U46619. The pulmonary vasodilator response to these agents was accompanied by a dose-related decrease of systemic arterial pressure. In decreasing lobar arterial pressure at elevated pulmonary vasomotor tone, the order of potency was nifedipine > verapamil > diltiazem, whereas in reducing systemic arterial pressure, the order of 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, verapamil 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 three calcium-channel-blocking agents blocked the pulmonary vasoconstrictor responses to BAY K 8644 (calcium entry promoter) and U46619 (thromboxane A(2) mimic). Nifedipine infusion also reduced the pulmonary vasoconstrictor responses to methoxamine and BHT933 (alpha(1)- and alpha(2)-adrenoceptor agonists, respectively), whereas verapamil infusion reduced the responses only to methoxamine. Infusion of diltiazem caused no significant decrease of responses to either alpha-adrenoceptor agonist. The results of the present study suggest that the dihydropyridine, nifedipine, is more potent than the non-dihydropyridines, verapamil and diltiazem, in reducing the pulmonary vascular resistance and more effective in inhibiting the vasoconstrictor responses to the alpha-adrenoceptor agonists, to U46619 and to BAY K8644 in the feline pulmonary circulation at the infusion rates which cause no or little hemodynamic changes.