Effects of inosine on adenosine-induced coronary vasodilation in the open chest dog

The effects of inosine (CAS 58-63-9) on adenosine-induced coronary vasodilation were studied in open-chest dogs. Inosine and hypoxanthine were infused into the coronary artery at a rate to obtain respective calculated coronary plasma concentrations of 10(-5) mol/l, and the dose-coronary flow response of adenosine was recorded with and without inosine or hypoxanthine infusion. When the maximum coronary dilation was obtained, 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 concentrations of either inosine or hypoxanthine. It was found that inosine, but not hypoxanthine, intensified the coronary vasodilatory effect of adenosine, which was abolished by 8-PT injection: EC50 of adenosine was reduced from 10(-5.43) mol/l to 10(-5.90) mol/l by inosine. Inosine and hypoxanthine did not affect adenosine deaminase activity at concentrations of 10(-4) mol/l or less. These findings indicate that inosine intensifies the coronary vasoactivity of adenosine, independent of inhibition of adenosine deaminase activity.