RENAL HEMODYNAMIC AND EXCRETORY EFFECTS OF N-0861, A NONXANTHINE ADENOSINE A(1)-RECEPTOR ANTAGONIST

The renal hemodynamic and excretory effects of intravenous N-0861, a n on-xanthine adenosine A(1)-receptor antagonist, were evaluated in cons cious and anesthetized male Sprague-Dawley rats. In conscious rats, N- 0861 (10, 30 mu mol/kg, iv) significantly increased the excretion of u rine, Na+, and K+; UClV was increased only in the rats treated with 10 mu mol/kg, N-0861. The relative excretion of K+ was similar to that o f Na+. Lower doses of N-0861 (1,3 mu mol/kg, iv) had no effect. During clearance studies in anesthetized rats, N-0861 (3, 10, 30 mu mol/kg, iv) had little effect on systemic or renal hemodynamics, but provoked significant saluresis that was poorly related to dose, and that was ch aracterized by a somewhat greater excretion of Na+ and Cl- relative to K+ These results indicate that the selective adenosine A(1) receptor antagonist N-0861 has little influence on resting renal hemodynamics a nd suggest that the natriuretic responses are due to inhibition of tub ular Na+ reabsorption. (C) 1994 Wiley-Liss, Inc.