Inhibition of hypoxic pulmonary vasoconstriction by dipyridamole and prostaglandin E₁ in the platelet depleted dog

Dipyridamole (D) and prostaglandin E₁ (P) are known to inhibit platelet aggregation and reduce hypoxic pulmonary vasoconstriction. The authors wished to see if the reduction of the pressor response was secondary to their effect on platelets, or due to a direct action on vascular smooth muscle. The number of circulating platelets was reduced (310±25 to 14±5 x 10³) by a platelet antiserum (AS) given to 6 dogs the day before the experiment. The hypoxic pressor response before and during administration of either D or P was compared in these dogs to the response of another 6 dogs with normal platelet counts (287±43 x 10³). D (4 mg/kg I.V.) and P (100 μg/min I.V.) did not alter the normoxic pulmonary vascular resistance, however, both significantly (P<0.01) reduced the pulmonary pressor response to hypoxia. The reduction of the hypoxic vasoconstriction in the virtual absence of circulating platelets suggests a direct action of D and P on vascular smooth muscle, which might be mediated by an increase of the cAMP level in hypoxic smooth muscle cells.