Natriuretic effect of adenosine A1-receptor blockade in rats

Abstract

Many effects of adenosine on renal function have been identified. The development of adenosine receptor blockers has made it possible to identify which of these effects are exerted by endogenous adenosine. At least four adenosine receptor subtypes, denoted A1, A2a, A2b, and A3 are currently known. In the present study the selective A1 receptor blocker 1,3-dipropyl-8[2-(5,6-epoxy) norbanyl] xanthine (CVT-117) was used to assess the effect of A1 activation by endogenous adenosine on renal function in rats. Clearance studies 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 administration of vehicle in time-control rats. Measurements of heart rate before and after administration of exogenous adenosine confirmed effective A1 receptor blockade. At both the lower and higher doses, A1 receptor blockade with CVT-117 increased fractional sodium excretion and urine flow rate without altering GFR. The increase in sodium excretion following A1 blockade was not accompanied by increases in the excretion of phosphate or potassium. These results show that endogenous adenosine promotes sodium retention by activation of A1 receptors.