Vascular effects of infused adenosine are not mediated by prostacyclin release in humans.
Adenosine may contribute to the regulation of tissue blood flow directly and via release of vasoactive substances. For example, in the isolated, perfused heart, the nucleoside has been reported to release prostacyclin, a potent vasodilator. In humans, minor variations in prostacyclin release into the circulation result in readily detectable changes in the urinary excretion of its metabolite, 2,3-dinor-6-ketoprostaglandin (PG) F1 alpha, as measured by negative ion-chemical ionization gas chromatography-mass spectrometry. To test the hypothesis that prostacyclin participates in or mediates the vascular effects of adenosine, we administered adenosine (5.1 mg/min) or vehicle to healthy volunteers in random order as a 2-h infusion into the femoral artery under double-blind conditions. The plasma levels of adenosine, inosine, and hypoxanthine increased significantly during infusion of active drug, but the urinary excretion of adenosine and uric acid were unchanged, implying efficient tissue uptake of the infused nucleoside. Adenosine, but not vehicle, significantly (P less than 0.01) increased leg blood flow (from 2.7 +/- 0.3 to 8.7 +/- 2.5 ml X 100 ml tissue-1 X min-1), heart rate (from 66 +/- 3 to 80 +/- 4 beats/min), and urinary epinephrine excretion (from 2.8 +/- 0.4 to 5.4 +/- 0.8 ng/mg creatinine). In contrast, the excretion of 2,3-dinor-6-keto-PGF1 alpha was unaltered by infusion of adenosine. We confirmed that biologically significant alterations in prostacyclin release in the lower limb vascular bed would be reflected by the urinary metabolite in experiments involving local infusion of prostacyclin at a rate below the threshold necessary to alter limb blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D000241:Adenosine / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D004837:Epinephrine / Q000652:urine; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000097:blood; D007288:Inosine / Q000097:blood; D007866:Leg / Q000098:blood supply; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D014527:Uric Acid / Q000097:blood
D007042:Hypoxanthines; D014527:Uric Acid; D019271:Hypoxanthine; D015121:6-Ketoprostaglandin F1 alpha; D007288:Inosine; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D011464:Epoprostenol; D000241:Adenosine; D004837:Epinephrine