The effects of arachidonic acid, PGI2, and 6-keto-PGF1 alpha on cyclic nucleotide concentrations in a ventilated and artificially perfused isolated dog lung.
In 35 isolated dog lung preparations, the pulmonary circulation of the right lung was completely separated from that of the left so that 1 lung of each preparation could serve as a control. The lungs were ventilated with 14% O2, 6% CO2 and 80% N2 and the pulmonary circulations were perfused with a dextran-salt-bicarbonate solution containing theophylline. Samples of perfusate were assayed for cyclic AMP and cyclic GMP (radioimmunoassay). Infusions of arachidonic acid (n=6) and PGI2 (n=4) but not 6-keto-PGF1 alpha (n=3) into the pulmonary circulation led to increases in cyclic AMP compared to control. Cyclic GMP levels were unchanged by the various infusions. Indomethacin (n=4) and acetylsalicylic acid (n=4) (prostaglandin (PG) synthesis inhibitors), and tranylcypromine (n=4) (a PGI2 synthetase inhibitor), prevented the cyclic AMP increases from arachidonic acid. This prevention was not the result of interference with the ability of cells to produce or release cyclic AMP since indomethacin (n=3), acetylsalicylic acid (n=3), and tranylcypromine (n=4) did not prevent cyclic AMP increases from PGI2. We conclude that infusion of arachidonic acid into the canine lung elevated pulmonary cyclic AMP but not cyclic GMP; that part or all of this increase most likely resulted from conversion of arachidonic acid to products of PG synthesis, particularly PGI2; that infusion of PGI2 mimicked arachidonic acid in that pulmonary cyclic AMP but not cyclic GMP was elevated, and that 6-keto-PGF1 alpha, a metabolite of PGI2, is unlikely to account for the cyclic AMP increases in this study.
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004285:Dogs; D011464:Epoprostenol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D010477:Perfusion; D011453:Prostaglandins / Q000494:pharmacology*; D014191:Tranylcypromine / Q000494:pharmacology
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D014191:Tranylcypromine; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP; D001241:Aspirin; D007213:Indomethacin