Effects of KW-3902, a selective and potent adenosine A(1) receptor antagonist, on renal hemodynamics and urine formation in anesthetized dogs

The purpose of the present investigation was to examine the effects of KW-3902 [8-(noradamantan-3-yl)-1,3-dipropyl-xanthine], a selective and potent adenosine A(1) receptor antagonist, in order to clarify the role of adenosine in the control of renal hemodynamics and urine formation in anesthetized dogs. KW-3902 was directly infused into the renal artery to eliminate the systemic effects of the drug. KW-3902 (10 mu g/kg/min) almost completely inhibited the renal vasoconstriction induced by adenosine via A(1) receptors. Intrarenal infusion of KW-3902 did not affect mean arterial pressure, renal blood flow, creatinine clearance, or arterial plasma renin activity, but drastically increased urine flow, urinary excretion of sodium, and osmolar clearance. Inhibition of the renin-angiotensin system using CV-11974 [2-ethoxy-1-((2'-(1-H-tetrazole-5-yl)biphenyl-4-yl)methyl)-1-H-benzimidazole-7-carboxylic acid], a selective AT(1) antagonist, did not affect the diuretic action of KW-3902. These data suggest that endogenous adenosine does not play a significant role in the control of renal hemodynamics in whole kidney, but that it plays an important role in preserving body fluid via the A(1) receptor independent of the renin-angiotensin system in anesthetized dogs.