Eicosanoids and hypoxic pulmonary vasoconstriction in normal man

Pulmonary haemodynamics and blood gas tensions were investigated in eight healthy volunteers, breathing room air and at the 15th min of an acute inspiratory hypoxia (fraction of inspired oxygen, (FIO2), 0.125) before and after administration of ibuprofen, a cyclooxygenase inhibitor, and of dazoxiben, a thromboxane A2 (TxA2) synthetase inhibitor; both drugs either with or without an infusion of prostaglandin E1. Hypoxia decreased arterial oxygen tension (PaO2) to below 50 mmHg in every subject and increased pulmonary vascular resistance by an average of 100-150% from baseline values. Acute and chronic dazoxiben or ibuprofen administration markedly reduced serum thromboxane B2 (TxB2), the stable metabolite of TxA2, but had no effect on pulmonary haemodynamics and blood gas tensions in both normoxic and hypoxic conditions. Prostaglandin E1 given in addition to ibuprofen or to dazoxiben did not inhibit hypoxia-induced increases in pulmonary vascular resistance. The stability of this hypoxic pressor response on repetition of an acute hypoxic exposure was established in six additional healthy subjects. Although obtained on a small number of subjects, these results do not suggest that products of the cyclooxygenase pathway of arachidonic acid metabolism play an important role in modulating normoxic or hypoxic pulmonary vascular tone in man.