Effect of YM435, a Dopamine DA 1 Receptor Agonist, in a Canine Model of Ischemic Acute Renal Failure

Abstract

1. The effects of (-)-( S)-4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline-7,8-diol monohydrochloride monohydrate (YM435), a dopamine DA1 receptor agonist, were evaluated in a canine model of ischemic acute renal failure (ARF). 2. ARF was induced by clamping the left renal artery for 1 hr and subsequent reperfusion of the left kidney in anesthetized uninephrectomized dogs. 3. After 1-hr complete renal artery occlusion, an intravenous infusion of either YM435 (0.3 μg/kg/min) or 0.9% saline (vehicle) was begun and continued for 1 hr. 4. In the vehicle group, renal ischemia markedly decreased glomerular filtration rate, urine flow and urinary sodium excretion. The YM435 group was characterized by significant recoveries in glomerular filtration rate, urine flow, and urinary sodium excretion as compared with the vehicle group. 5. These results indicate that YM435 can facilitate recovery in glomerular filtration rate, urine flow, and urinary sodium excretion in a canine model of ARF induced by ischemia. YM435 may be useful in the preservation of renal function in ischemia-induced ARF.