RENAL EFFECT OF YM435, A NEW DOPAMINE D-1 RECEPTOR AGONIST, IN ANESTHETIZED DOGS

The renal effects of YM435 enyl)-7,8-dihydroxy-1,2,3,4-tetrahpdroisoqu inoline hydrochloride hydrate), a dopamine D-1 receptor agonist, were investigated in anesthetized does. Intravenous infusion of YM435 (0.1- 3 mu g/kg per min) increased renal blood flow and decreased mean blood pressure in a dose-dependent manner with little effect on heart rate. Glomerular filtration rate, urine flow and urinary sodium excretion w ere concomitantly increased. The renal effect of YM435 by intravenous infusion at 0.3 mu g/kg per min was completely blocked by treatment wi th the selective dopamine D-1 receptor antagonist SCH 23390 hyl-1-phen yl-2,3.4,5-tetrahydro-(1H)-3-benzazepine hydrochloride). Furthermore, intravenous infusion of YM435 (0.3 mu g/kg per min) reversed the angio tensin II-induced decreases in renal blood flow, glomerular filtration rate, urine flow and urinary sodium excretion, and prevented the decr ease in renal blood flow, glomerular filtration rate and urine flow in duced by renal nerve stimulation and platelet-activating factor (PAF). These results suggest that intravenous administration of YM435 produc es renal vasodilating and diuretic/natriuretic effects by stimulation of dopamine D-1 receptors, and demonstrate that YM435 can inhibit angi otensin II-, renal nerve stimulation- and PAF-induced renal dysfunctio n. (C) 1997 Elsevier Science B.V.