Thromboxane synthetase inhibition and pulmonary response to hypoxia in conscious adult sheep.

This study investigated the effects of a thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (ketoprofen) on hypoxic pulmonary vasoconstriction in conscious adult sheep in order to evaluate the physiological role of thromboxane and other cyclooxygenase products. In addition, we studied the effects of histamine H1 (chlorpheniramine) and H2 antagonists (cimetidine) on hypoxic pulmonary vascular tone. Hypoxia caused a 37% rise in pulmonary arterial pressure (p less than 0.05) and a 36% increase in pulmonary vascular resistance (p less than 0.05). Pretreatment with intravenous OKY-046 10 mg/kg or ketoprofen 2 mg/kg had no effect on normoxic pulmonary vascular tone and inhibited the increase in plasma TXB2 concentration during hypoxia without affecting the pulmonary pressor response to hypoxia. Cimetidine produced an increase in hypoxic pulmonary vascular tone when individual members of the group were compared, but there was no statistically significant difference when the group was compared to the control study. Chlorpheniramine had no effect on hypoxic pulmonary tone. These data suggest that hypoxic pulmonary vasoconstriction is not mediated by release of TXA2, that hypoxic vascular tone is not modulated by cyclooxygenase products, and that the histamine H2 receptor may play a modulating role in hypoxic pulmonary vasoconstriction in conscious adult sheep.