title: Moderation of hypoxic vasoconstriction by infused arachidonic acid: role of PGI2.
abstract: To determine the role of prostaglandins in modulating pulmonary circulatory responses, we examined the effect of the prostaglandin precursor, sodium arachidonate, on the pulmonary vascular resistance of mongrel dogs during alveolar hypoxia. When infused intravenously for 5 min during hypoxia, sodium arachidonate (1 mg/min) decreased pulmonary vascular resistance from 6.9 +/- 1.1 to 4.9 +/- 0.6 U (P less than 0.05). The vasodilation produced by sodium arachidonate was blocked by sodium meclofenamate, a cyclooxygenase inhibitor. By infusing radiolabeled sodium arachidonate and collecting aortic blood samples, we found from chromatographic and mass spectrometric analysis that a major prostaglandin produced was 6-keto-PGF1 alpha, the stable hydrolysis product of PGI2. Infusion of PGI2, but not PGE2, during hypoxia decreased pulmonary vascular resistance. We concluded that the prostaglandin precursor, sodium arachidonate, is a vasodilator of the pulmonary vasculature that has been constricted by alveolar hypoxia, probably because PGI2 is formed from the arachidonate. The pulmonary circulation may be similar to the systemic circulation where vasoconstriction results in the generation of vasodilatory prostaglandins that attenuate the constrictor effect.
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D004285:Dogs; D011464:Epoprostenol / Q000502:physiology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000139:chemically induced*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D011460:Prostaglandins F / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001095:Arachidonic Acids; D011453:Prostaglandins; D011460:Prostaglandins F; D008469:Meclofenamic Acid; D011464:Epoprostenol