DIURETIC AND SALIURETIC EFFECTS OF 1,3-DIPROPYL-8-CYCLOPENTYLXANTHINE, A SELECTIVE ADENOSINE-A1-RECEPTOR ANTAGONIST

We have previously shown that 8-phenyltheophylline (8-PT), a non-selective antagonist at adenosine A1- and A2- receptors, has a diuretic effect. In this study, the diuretic and adenosine antagonist effects of the A1-receptor selective compound 1,3-dipropyl-8-cyclopentylxanthine (CPX) have been examined in the conscious rat. CPX (0.1 and 0.3 mg kg-1 i.v.) significantly attenuated bradycardic but not hypotensive responses evoked by adenosine. In contrast, 8-PT (3 mg kg-1 i.v.) significantly antagonized both adenosine-induced bradycardia and hypotension. CPX (0.1 and 0.3 mg kg-1 i.v.) evoked a dose-related diuretic and saliuretic response in the conscious rat. These results indicate that the diuretic effects of adenosine antagonists are associated with blockade of the A1-receptor sub-type.