Renal effect of YM435, a new dopamine D1 receptor agonist, in anesthetized dogs

The renal effects of YM435 ((-)-(S)-4-(3,4-dihydroxyphenyl)-7,8-dihydroxy -1,2,3,4-tetrahydroisoquinoline hydrochloride hydrate), a dopamine D1 receptor agonist, were investigated in anesthetized dogs. Intravenous infusion of YM435 (0.1-3 micrograms/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 were concomitantly increased. The renal effect of YM435 by intravenous infusion at 0.3 microgram/kg per min was completely blocked by treatment with the selective dopamine D1 receptor antagonist SCH 23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazep ine hydrochloride). Furthermore, intravenous infusion of YM435 (0.3 microgram/kg per min) reversed the angiotensin II-induced decreases in renal blood flow, glomerular filtration rate, urine flow and urinary sodium excretion, and prevented the decrease in renal blood flow, glomerular filtration rate and urine flow induced by renal nerve stimulation and platelet-activating factor (PAF). These results suggest that intravenous administration of YM435 produces renal vasodilating and diuretic/natriuretic effects by stimulation of dopamine D1 receptors, and demonstrate that YM435 can inhibit angiotensin II-, renal nerve stimulation- and PAF-induced renal dysfunction.