Implications of the Coronary Vascular Endothelium as Mediator of the Vasodilatory and Dromotropic Actions of Adenosine

Recent studies have shown that the vasodilatory response of adenosine is partially endothelium dependent. Therefore, to further characterize the physiologic role of the vascular endothelium as mediator of adenosineʹs cardiovascular effects, we have examined in isolated perfused guinea-pig hearts the dromotropic and vascular effects of adenosine in the presence of the adenosine antagonist, XAC, covalently conjugated to latex microspheres of 0.07 μm diameter. Our results demonstrate that intravascular infusion of the microsphere XAC conjugates abolishes the vasodilatory and negative dromotropic effects of infused adenosine, and inhibits the dromotropic effects of hypoxia. As these particles because of their size remain intravascularly confined, we conclude that the dromotropic and vasodilatory effects of exogenous adenosine, and the dromotropic effects of hypoxia (endogenous adenosine), arise from the intravascular adenosine compartment acting by way of the vascular endothelium. In addition, while neither the temporal course of vasodilation nor the steady state of vasodilation cause by hypoxia were influenced by unconjugated XAC, our results do show that the microsphere XAC conjugate increase the time necessary for maximum vasodilation to occur during hypoxia.