NATRIURETIC EFFECT OF ADENOSINE A(1)-RECEPTOR BLOCKADE IN RATS

Background. Many effects of adenosine on renal function have been iden tified. The development of adenosine receptor blockers has made it pos sible to identify which of these effects are exerted by endogenous ade nosine. At least four adenosine receptor subtypes, denoted A(1), A(2a) , A(2b), and A(3) are currently known. In the present study the select ive A(1) receptor blocker 1,3-dipropyl-8 [2-(5,6-epoxy) norbanyl] xant hine (CVT-117) was used to assess the effect of A(1) activation by end ogenous adenosine on renal function in rats. Methods. Clearance studie s were performed before and after administration of 0.1 mg/kg and 0.8 mg/kg of CVT-117 in separate groups of rats and before and after admin istration of vehicle in time-control rats. Measurements of heart rate before and after administration of exogenous adenosine confirmed effec tive A(1) receptor blockade. Results. At both the lower and higher dos es, A(1) receptor blockade with CVT-117 increased fractional sodium ex cretion and urine flow rate without altering GFR. The increase in sodi um excretion following A(1) blockade was not accompanied by increases in the excretion of phosphate or potassium. Conclusion. These results show that endogenous adenosine promotes sodium retention by activation of A(1) receptors.