Inhibition of hypoxic pulmonary vasoconstriction by nifedipine

Nifedipine is a potent slow channel calcium antagonist and systemic vasodilator recently reported to attenuate hypoxic pulmonary vasoconstriction in man. Other systemic vasodilators have also been shown to attenuate hypoxic pulmonary vasoconstriction, but their effects in some species may be mediated by reflex beta-adrenergic discharge. We evaluated the effect of nifedipine on the relation between pulmonary arterial pressure and blood flow during hyperoxia (inspired partial pressure of oxygen [PO2] 200 mm Hg) and hypoxia (inspired PO2 50 mm Hg) in denervated ventilated pig lungs perfused in situ with the animal's own blood. Ten lungs were ventilated with alternating 15 minute periods of hyperoxia and hypoxia. Hypoxia shifted the pulmonary artery pressure (x axis)-blood flow (y axis) relationship to the right and decreased its slope, indicating vasoconstriction. Nifedipine, given as a 0.1, 1, or 10 microgram/kg bolus into the pulmonary artery, caused a dose-dependent reduction of hypoxic pulmonary vasoconstriction. It is concluded that nifedipine is a potent pulmonary vasodilator acting locally within the lung and that it might be useful in the therapy of hypoxic pulmonary hypertension from chronic lung disease in man.