Arachidonic acid metabolism by neonatal lungs perfused with Krebs bicarbonate buffer.
We characterized and quantified products of exogenous arachidonic acid metabolism by neonatal lamb lungs perfused with Krebs solution and determined effects of alveolar hypoxia upon this metabolism. The predominant metabolite was PGI2 (62.4 +/- 5.8 (SEM)% of the total prostanoids (PGs) produced). An additional 23.1 +/- 6.7% was metabolized PGI2. PGE2 (1.7 +/- 3.0%) was produced also. Little thromboxane B2 (TXB2) (3.3 +/- 1.7%) was synthesized by these platelet-free lungs. Although the pulmonary vasoconstrictor response to arachidonic acid infusion reached a plateau in 71 +/- 19 seconds, the PG efflux was greater 8-15 minutes after beginning arachidonic acid infusion (3066 +/- 1353 ng/min) than 1-8 minutes into the infusion (899 +/- 343 ng/min). Reduction of FIO2 from 20% to 3% O2 which produces vasoconstriction in the absence of exogenous arachidonic acid, did not alter the PG profile nor quantity produced. With respect to the neonatal lamb pulmonary vasculature perfused with Krebs solution, we conclude: 1) exogenous arachidonic acid ultimately is metabolized predominantly to PGI2, 2) arachidonic acid-induced pulmonary vasoconstriction is not caused by TXA2, 3) short term hypoxia does not alter the conversion of excess arachidonic acid to PGs, and 4) a lag between intrapulmonary PG synthesis and pulmonary venous efflux may occur.
D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001639:Bicarbonates / Q000494:pharmacology; D002021:Buffers; D011464:Epoprostenol / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D012756:Sheep; D013928:Thromboxane A2 / Q000494:pharmacology; D014661:Vasoconstriction
D001095:Arachidonic Acids; D001639:Bicarbonates; D002021:Buffers; D011453:Prostaglandins; D016718:Arachidonic Acid; D013928:Thromboxane A2; D011464:Epoprostenol