Role of Ecto-5′-Nucleotidase on Hypoxia-Induced Adenosine Formation in the Perfused Guinea Pig Heart

Abstract

The role of adenosine in the transmyocardial effluent, which was obtained by the method of De Deckere and Ten Hoor on the regulation of coronary flow, was examined in the perfused guinea pig heart. EHNA, an adenosine deaminase inhibitor, was used for changing adenosine concentration in the fluid. It was found that there was a good correlation between adenosine concentration in the transmyocardial effluent and the coronary flow. Using the same method, the role of ecto-5′-nucleotidase on the hypoxia (60% O2)-induced adenosine formation was reinvestigated. In hypoxia, the adenosine concentration in the transmyocardial effluent was increased together with the coronary flow, and the regression line representing the relation between the adenosine concentration and the coronary flow coincided with the same correlation obtained after EHNA treatment under normoxia, indicating that adenosine in the transmyocardial effluent plays an important role in the regulation of the coronary flow. Since the hypoxia-induced increase in the adenosine formation was inhibited by AOPCP, a specific inhibitor of the ecto-5′-nucleotidase, it was suggested that the majority of the hypoxia-induced adenosine formation in the guinea pig heart was via the pathway of ecto-5′-nucleotidase. Furthermore, it was found that AOPCP caused an increase in AMP concentration in the transmyocardial effluent which was unassociated with an increase in coronary flow. Thus, it seems very likely that endogenous AMP has only a very weak or no vasodilatatory activity and its apparent vasoactivity was due to its conversion to adenosine.