Attenuation of Hypoxic Pulmonary Vasoconstriction by Verapamil in Intact Dogs

SummaryThe hypothesis that hypoxic pulmonary vasoconstriction is mediated directly by depolarization of the vascular smooth muscle was tested in anesthetized dogs. Pulmonary vascular responses to hy-poxia were first determined in eight dogs during 20-min exposures to 10% O2. Each animal was then treated with verapamil (0.5 mg/kg, iv), to block transmembrane Ca2+ influx in an attempt to abolish the vasoconstrictor responses to hypoxia. The hypoxic exposures were then repeated, and the pulmonary vascular responses were compared to the control responses. Verapamil administration attenuated hypoxic pulmonary vasoconstriction, but did not abolish the responses to hypoxia. Pulmonary vascular resistance increased 87% during the control hypoxic exposure, but increased only 38% during hypoxia after verapamil. The response to another vasoconstrictor, prosta-glandin F2α, was not reduced by verapamil, indicating a different mechanism of mediation. These results suggest that the pulmonary vasoconstrictor response to a...