Comparative effects of nifedipine, verapamil, and diltiazem on experimental pulmonary hypertension

The role of calcium-channel blocking agents in the treatment of pulmonary hypertension is not well defined. Consequently, the effects of diltiazem, nifedipine, and verapamil were compared in 3 groups of anesthetized dogs (n = 6 for each group). In each group, normoxic hemodynamic variables were recorded before and after increasing doses of diltiazem, nifedipine, and verapamil (5 × 10^-8 M/kg, low; 10^-7 M/kg, medium; and 10^-6 M/kg, high dose; given intravenously over 2 minutes). In addition, the effect of these doses on the pulmonary pressor responses to hypoxia (fractional inspired oxygen concentration [FIO₂] 12%) and prostaglandin F_2α (PGF_2α) (5 μg/kg/min, intravenously for 4 minutes) was measured. During normoxia, high-dose nifedipine and verapamil decreased mean aortic pressure and systemic vascular resistance while increasing cardiac output in all dogs in both groups (p <0.01). Pulmonary vascular resistance, however, remained unchanged. High-dose diltiazem did not significantly alter cardiac output or pulmonary vascular resistance. During acute hypoxic pulmonary hypertension, verapamil decreased cardiac output by 30% (p <0.01) without appreciably altering pulmonary arterial pressure; thus pulmonary vascular resistance increased slightly (4.9 ± 0.6 to 6.4 ± 1.0 mm Hg/liter/min, difference not significant [NS]). Nifedipine decreased hypoxic pulmonary vascular resistance to normoxic values (p <0.01). Cardiac output increased 71% while pulmonary arterial pressure remained unchanged. Diltiazem administration produced no change in hypoxic pulmonary hemodynamic variables. The responses to diltiazem, nifedipine, and verapamil during acute pulmonary vasoconstriction induced by PGF_2α were similar to those induced by hypoxia. After verapamil, pulmonary vascular resistance tended to increase (7.3 ± 1.3 to 8.1 ± 1.4 mm Hg/liter/min, NS). Nifedipine, however, completely blocked pulmonary vasoconstriction by decreasing pulmonary vascular resistance to pre-PGF_2α levels (p <0.01). This was accompanied by a 157% increase in cardiac output and only a small increase in pulmonary arterial pressure (7 mm Hg). Again, diltiazem produced no change in pulmonary hemodynamic variables. In these acute studies, nifedipine appeared to be a more effective pulmonary vasodilator than verapamil or diltiazem.