Release of prostacyclin from the human pulmonary vascular bed in response to cholinergic stimulation.
The ability of the human pulmonary vascular bed to synthesize prostaglandins (PGs) in response to cholinergic stimulation was investigated in healthy male volunteers. In all of them, except controls, carbaminoylcholine (CCh) was injected subcutaneously at a dose of 5 micrograms/kg. In 3 subjects [1-14C]-labelled arachidonate was then infused at a constant rate into the right atrium between 10 and 15 min after the administration of the drug and the blood from the subclavian artery was sampled simultaneously. The arterial content of [14C]-labelled metabolites was extracted, separated by thin-layer chromatography and quantified using liquid scintillation spectrometry. In 8 other subjects PGI2-like activity after the administration of CCh was assayed in the arterial blood and in 1 subject in the venous blood, using a technique for continuous measurement of platelet aggregation on blood-superfused collagen strip. The major portion of [14C]-activity in the radiochromatograms migrated in parallel with the 6-keto-PGF1 alpha standard. No early defined peaks corresponding to any of the unlabelled PGs D2, E2 or F2 alpha, appeared, but in one chromatogram a minor radiopeak corresponding to authentic thromboxane B2 was observed. Also in the platelet aggregation experiments, 5-15 min after the administration of CCh, a significant increase in the PGI2-like activity was observed in the arterial as well as in the peripheral venous blood, which effect of the drug was abolished by pretreatment with atropine and acetylsalicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D011464:Epoprostenol / Q000097:blood / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000294:innervation / Q000378:metabolism*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000502:physiology*
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D002217:Carbachol; D011464:Epoprostenol