Diuretic effects of KW-3902, a novel adenosine A1-receptor antagonist, in anesthetized dogs.

Abstract

The effects of intravenous infusion of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel adenosine A1-receptor antagonist, on urine volume, urinary excretion of electrolytes and renal hemodynamics were examined in anesthetized dogs. KW-3902 at 10 and 30 micrograms/kg/min for 20 min inhibited the decline of renal blood flow induced by intrarenal arterial injection of adenosine (0.5-2.0 micrograms). KW-3902 at these doses produced significant increases in urine volume and sodium excretion with little change in potassium excretion. The diuretic effect of KW-3902 at 30 micrograms/kg/min for 20 min continued for longer than 1 h even after discontinuation of the KW-3902 infusion. KW-3902 did not affect creatinine clearance, renal blood flow, arterial blood pressure or heart rate. Furosemide at 10 micrograms/kg/min for 20 min brought about significant increases in urine volume and excretion of sodium and potassium. The diuresis and saliuresis induced by furosemide continued for only 40 min after discontinuation of the drug infusion. Trichlormethiazide at 3 micrograms/kg/min for 20 min also provoked increases in urine volume and sodium excretion, but did not affect potassium excretion. The diuretic and natriuretic effect of trichlormethiazide gradually disappeared after discontinuation of the drug infusion. The present study in anesthetized dogs suggests that KW-3902, an adenosine A1-receptor antagonist, produces diuresis and natriuresis but not kaliuresis and that the diuresis and natriuresis are caused in large part by the inhibition of sodium reabsorption at tubular sites.