Conversion of exogenous arachidonic acid to prostaglandins in the pulmonary circulation in vivo. A human and animal study.
The capacity of human lungs to synthetize prostaglandins (PGs) from exogenous arachidonic acid (AA) was investigated in healthy male volunteers. 14C-labelled AA was infused at a constant rate into the right atrium under simultaneous sampling of blood from the ascending aorta. The arterial content of 14C-AA metabolites was extracted, separated with thin-layer chromatography and quantified using fractionated liquid scintillation spectrometry. Conversion of exogenous AA to prostacyclin (PGI2) was also studied in the lungs of anaesthetized cats. In these experiments different doses of unlabelled AA were administered intravenously. Simultaneously PGI2-activity in the arterial blood was assayed using a technique for continuous measurement of platelet aggregation on blood superfused collagen strip. Radiochromatograms of the human arterial plasma revealed no clearly defined peaks corresponding to any of the unlabelled standards of PGD2, PGE2, 6-keto-PGF1 alpha, PGF2 alpha or TxB2. The 14C-activity in the chromatograms materialized only in one (apart from AA) prominent peak in parallel to 13,14-dihydro-15-keto-PGE2. Neither in cats did significant amounts of PGI2 appear in the arterial blood after administration of AA in moderate doses. Only very high AA doses caused a slight increase in arterial PGI2-activity. The results demonstrate that human lungs do not convert exogenous AA to PGs under physiological conditions. In cats the reluctance of the lungs to utilize exogenous precursor can only be overcome with high, non-physiological AA doses. The data may suggest the existence of special regulatory mechanisms which control release of PGs from the lungs and promote utilization of endogenous precursor.
D000328:Adult; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000378:metabolism*; D002415:Cats; D002855:Chromatography, Thin Layer; D011464:Epoprostenol / Q000097:blood / Q000494:pharmacology; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis* / Q000097:blood; D011652:Pulmonary Circulation
D001095:Arachidonic Acids; D011453:Prostaglandins; D011464:Epoprostenol