Effects of indomethacin on estradiol-induced attenuation of hypoxic vasoconstriction in lamb lungs

To determine whether cyclooxygenase products mediated the attenuation of hypoxic pulmonary vasoconstriction induced by estradiol, we measured pulmonary arterial pressure at a flow of 50 ml·min^-1·kg^-1 (Ppa₅₀) during steady-state exposures to inspired O₂ tensions (PIO₂) between 0 and 200 Torr in isolated lungs of juvenile ewes. Intramuscular estradiol (10 mg) 44-60 h before study significantly decreased perfusate concentrations of 6-ketoprostaglandin F(1α) (6-keto-PGF(1α)), the stable metabolite of the pulmonary vasodilator, prostacyclin, but did not significantly affect the stimulus-response relationship between PI(O₂) and Ppa₅₀. Estradiol (20 mg) 3-5 days before study increased 6-keto-PGF(1α) concentrations and decreased Ppa₅₀ at PI(O₂) of 10, 30, and 50 Torr. Indomethacin added to the perfusate of these lungs reduced 6-keto-PGF(1α) to undetectable levels and altered the estradiol-induced attenuation, increasing Ppa₅₀ at PI(O₂) of 10 and 30 Torr, but decreasing Ppa₅₀ at PI(O₂) of 200 Torr. Despite these effects, Ppa₅₀ remained lower than the values measured in lungs not treated with estradiol. These results suggest that the estradiol-induced attenuation of the hypoxic stimulus-response relationship was mediated only in part by cyclooxygenase products, the net effects of which were vasodilation at PI(O₂) of 10 and 30 Torr, but vasoconstriction at PI(O₂) of 200 Torr.