Release of vasodilator prostaglandin, PGI2, from isolated rat lung during vasoconstriction.
Prostaglandins are generated by the lungs and released into the circulation. Since inhibitors of prostaglandin synthesis enhance hypoxic pulmonary vasoconstriction, we wondered whether vasodilator prostacyclin was synthesized by the lungs in response to vasoconstriction. To test this hypothesis, we measured vasoconstriction induced by angiotensin II in isolated rat lungs before and after inhibition of prostaglandin synthetase. We found that sodium meclofenamate enhanced and prostacyclin and its precursor arachidonate abolished pulmonary vasoconstriction. In lungs labeled with 14C-arachidonate, effluent radioactivity increased after angiotensin II-induced vasoconstriction. Hypoxic vasoconstriction, but not hypoxia per se, caused an increase in lung effluent radioactivity. Chromatographic analysis of lung effluent showed that 6-keto-prostaglandin F1 alpha was the major arachidonic acid metabolite released during pulmonary vasoconstriction. We concluded that prostacyclin is produced by the lungs in response to vasoconstriction. Hypoxia per se seems not to be the adequate stimulus for enhanced lung prostacyclin formation. Lung prostacyclin may protect the pulmonary circulation against excessive vasoconstriction.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis* / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D010100:Oxygen / Q000502:physiology; D010477:Perfusion; D011453:Prostaglandins / Q000096:biosynthesis*; D011651:Pulmonary Artery / Q000502:physiology; D051381:Rats; D012965:Sodium Chloride; D014661:Vasoconstriction
D001095:Arachidonic Acids; D011453:Prostaglandins; D000804:Angiotensin II; D012965:Sodium Chloride; D008469:Meclofenamic Acid; D011464:Epoprostenol; D010100:Oxygen