D. Saito et al., EFFECTS OF INOSINE ON ADENOSINE-INDUCED CORONARY VASODILATION IN THE OPEN-CHEST DOG, Arzneimittel-Forschung, 43-2(9), 1993, pp. 950-953
The effects of inosine (CAS 58-63-9) on adenosine-induced coronary vas
odilation were studied in open-chest dogs. Inosine and hypoxanthine we
re infused into the coronary artery at a rate to obtain respective cal
culated coronary plasma concentrations of 10(-5) mol/l, and the dose-c
oronary flow response of adenosine was recorded with and without inosi
ne or hypoxanthine infusion. When the maximum coronary dilation was ob
tained, 10 ml of 2 x 10(-3) mol/l 8-phenyltheophylline (8-PT) solution
was injected into the femoral vein. Additionally, adenosine deaminase
activity was measured in vitro in the presence of various concentrati
ons of either inosine or hypoxanthine. It was found that inosine, but
not hypoxanthine, intensified the coronary vasodilatory effect of aden
osine, which was abolished by 8-PT injection: EC50 of adenosine was re
duced from 10(-5.43) mol/l to 10(-5.90) mol/l by inosine. Inosine and
hypoxanthine did not affect adenosine deaminase activity at concentrat
ions of 10(-4) mol/l or less. These findings indicate that inosine int
ensifies the coronary vasoactivity of adenosine, independent of inhibi
tion of adenosine deaminase activity.