Oxygen-induced vasodilation in pulmonary arterioles from fetal rats

Background. Oxygen is a potent stimulus for pulmonary vasodilation in the perinatal period. Little information is available regarding mediators of oxygen-induced pulmonary vasodilation in fetal rats. We have investigated the effect of blocking several proposed mediators of oxygen-induced vasodilation on the responses of isolated, third-generation pulmonary arterioles from term fetal rats to an increase in oxygen tension. Materials and methods. Third-generation pulmonary arterioles were isolated from fetal rats at term, Arterioles mere preconstricted by suffusion with "hypoxic" (pO(2) 25-40 mm Hg) solution containing 40 mM KCl. The vasodilation induced by suffusion with "normoxic" (pO(2) 90-150 mm Hg) 40 mM KCl solution was recorded for control pulmonary arterioles and for arterioles pretreated with inhibitors of nitric oxide synthase and cyclooxygenase, and blockers of bradykinin receptors and purinergic receptors, Responses to oxygen suffusion were also recorded for pulmonary arterioles denuded of endothelium. Results. Control arterioles dilated 113 +/- 28% of the potassium-induced preconstriction after 60 min of normoxic suffusion. Pretreatment with indomethacin completely blocked oxygen-induced vasodilation. Inhibitors of nitric oxide synthase, blockers of bradykinin and purinergic receptors, and removal of the endothelium did not significantly change normoxic vasodilation. Conclusions. Our results are most consistent with a vasodilator product of cyclooxygenase metabolism as a primary stimulus for oxygen-induced vasodilation in isolated, third-generation pulmonary arterioles from fetal rats. (C) 2000 Academic Press.