Hydralazine does not inhibit canine hypoxic pulmonary vasoconstriction

Clinical experience with hydralazine has led to conflicting data concerning its effect on the pulmonary vasculature. We studied the effects of hydralazine on the hypoxic pulmonary vasoconstrictor response in 9 dogs challenged with inhalation of 10% oxygen in the presence and absence of hydralazine. Prior to administration of the drug, hypoxia increased cardiac output from 174 +/- 13 to 209 +/- 21 ml/kg/min (p less than 0.05) and pulmonary artery pressure from 9 +/- 1 to 19 +/- 1 mmHg (p less than 0.05). After hydralazine, cardiac output rose during normoxia to 275 +/- 30 and during hypoxia to 305 +/- 34 ml/kg/min (p less than 0.05). Pulmonary artery pressure continued to respond to hypoxia, rising from 11 +/- 1 to 21 +/- 1 mmHg (p less than 0.05) in the presence of hydralazine. Hydralazine reduced pulmonary vascular resistance during normoxia from 173 +/- 14 to 136 +/- 13 dynes X s X cm-5 (p less than 0.05) but even after the drug, pulmonary vascular resistance rose sharply during hypoxia. There was no significant difference in the response to hypoxia of pulmonary artery pressure or pulmonary vascular resistance after hydralazine when compared with that before hydralazine. In a second set of 6 dogs, we repeated these experiments but volume-depleted the dogs after the administration of hydralazine to prevent the passive pulmonary vasodilation that occurs because of the rise in cardiac output with the drug. We again found no inhibition of hypoxic pulmonary vasoconstriction by hydralazine. Finally, we administered sodium nitroprusside to 4 dogs using the same model and found a significant inhibition of hypoxic pulmonary vasoconstriction. Hydralazine, unlike nitroprusside, does not inhibit the pulmonary vascular response to hypoxia.