Functional role of intravascular coronary endothelial adenosine receptors.

The endothelium is relatively 'impermeable' to adenosine. In addition, infusion of adenosine deaminase and transient infusion of large size adenosine agonists (molecular weight 100 kD) which are confined to the intravascular space depress effects of endogenous adenosine and retain physiologic activity respectively. Accordingly, the concept that intravascular adenosine may exert some of its action on the capillary lumen was tested by coupling the agonists: N6-([aminoethylamino]carbonyl)methylphenyladenosine (ADAC) and N6-octylamine adenosine (NOA) to carboxylated latex microspheres (0.07 microns diameter); thus, insuring their intravascular confinement. Our results demonstrated that sustained infusion of these particles into isolated saline perfused guinea pigs hearts caused a decrease in coronary vascular resistance, ventricular contraction, spontaneous ventricular rhythm, inhibition of auricular ventricular transmission and glycolytic flux. These effects were reversible and specific since microspheres without purines had no effect and the adenosine antagonist sulphophenyltheophylline blocked these responses. Furthermore, the effects were not the result that during the passage of the sphere-agonist complex through the heart the covalent bond hydrolyzed, releasing free agonist. Our data indicate that selective activation of intravascular coronary purine receptors may cause the release of endothelial bioactive messengers that regulate the function and metabolism of vascular and cardiac cells.