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 X 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 F2 alpha (PGF2 alpha) (5 micrograms/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 less than 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 less than 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 less than 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 PGF2 alpha 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-PGF2 alpha levels (p less than 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.