AJP - Heart and Circulatory Physiology, Vol 252, Issue 3 598-H604, Copyright © 1987 by American Physiological Society
Vascular effects of infused adenosine are not mediated by prostacyclin release in humans
J. Nowak, M. Wennmalm, A. Edlund, A. Wennmalm and G. A. Fitzgerald
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)
