Effects of hyperoxia and hypoxia on vascular prostacyclin formation in vitro.
Exposure to high oxygen (O2) concentrations, especially in the neonate, is associated with the development of pathologic syndromes characterized by vascular involvement including the retinopathy of prematurity. Some of the initial vascular changes observed appear consistent with a reduction in prostacyclin formation. Exposure of human umbilical arteries to oxygen resulted in more than 30% inhibition in the ability of the vessels to produce prostacyclin either from endogenous stores of arachidonic acid or from exogenously provided substrate. In contrast, hypoxia (which more closely approximates the fetal environment) resulted in more than 30% stimulation in the production of prostacyclin from either endogenous or exogenous arachidonic acid. When microsomes were prepared from treated arterial segments, these effects persisted. In vitro results suggest that neonates exposed to O2 after delivery may experience a marked decrease in vascular prostacyclin formation. Inhibition of the production of this potent vasodilator and antithrombotic metabolite could play an important role in the acute exudative phase of O2 toxicity.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D015237:Dinoprost; D015232:Dinoprostone; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D012178:Retinopathy of Prematurity / Q000209:etiology; D013929:Thromboxane B2 / Q000096:biosynthesis; D014469:Umbilical Arteries / Q000378:metabolism
D001095:Arachidonic Acids; D011458:Prostaglandins E; D011460:Prostaglandins F; D002084:Butylated Hydroxytoluene; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D010100:Oxygen