ADENOSINE, THEOPHYLLINE, AND PERFUSATE PH IN ISOLATED, PERFUSED GUINEA-PIG HEART

We have investigated, in isolated, perfused, spontaneously beating guinea pig hearts, the influence of perfusate pH on the coronary vasodilation produced by exogenous adenosine and on the inhibition of adenosine vasodilation by theophylline. Perfusate pH 7.20 and 6.89, produced by increasing P(CO2), reduced the concentration at which adenosine produced a response. Furthermore, the flow increment in response to higher adenosine concentrations was greater at pH 6.89 and less at pH 7.69 than at pH 7.42. The flow responses to alterations in pH was greater in the presence of adenosine (5 x 10-7 M) than in its absence. Theophylline, in amounts which by themselves were without effect on coronary flow, partially inhibited coronary vasodilation caused by adenosine both at pH 7.43 and 7.20. Our findings indicate that the coronary vasodilation produced by adenosine is pH sensitive but attenuation of this dilation by theophylline is not, at the values of pH tested. We conclude that theophylline's inability to regularly attenuate reactive hyperemia might be related to enhanced adenosine dilation caused by increased tissue hydrogen ion activity. Furthermore, the hydrogen ion might participate in coronary flow regulation in part via this interaction with adenosine.