Cyclooxygenase inhibition and effects of hypoxia on pulmonary circulation and gas exchange in anesthetized dogs

To investigate whether endogenously produced prostanoids are involved in hypoxic pulmonary vasoconstriction, pulmonary hemodynamic and gas exchange parameters and eicosanoid metabolites were measured in 5 anesthetized, artificially ventilated dogs (mean body weight 27 kg). Hypoxia elicited pulmonary vasoconstriction, but blood plasma levels of thromboxane B₂ (TXB₂) and 6-keto-prostaglandin F_1α (6kPGF_1α) (stable metabolites of TXA₂ and prostaglandin I₂, respectively) remained unchanged. Administration of the cyclooxygenase inhibitor indomethacin blocked the synthesis of prostanoids, so that 6kPGF_1α and TXB₂ levels decreased to values below the detection level (10 pg·ml⁻¹) both during normoxia or hypoxia, but did not affect pulmonary vascular resistance or the alveolar-arterial P_O2 difference (Pai - Pa)_O2. The pulmonary vascular bed remained, however, responsive to TXA₂ as evidenced by infusion of the TXA₂ mimetic, U 46619, which significantly increased the pulmonary vascular resistance and (Pai - Pa)_O2. Our data suggest that prostanoids are not involved in eliciting the effects of hypoxia on pulmonary hemodynamics and gas exchange efficiency.