多巴胺DA1受体激动剂YM435在犬缺血性急性肾衰竭模型中的作用

Effect of YM435, a dopamine DA1 receptor agonist, in a canine model of ischemic acute renal failure.

Yatsu T, Arai Y, Takizawa K, Kasai-Nakagawa C, Takanashi M, Uchida W, Inagaki O, Tanaka A, Takenaka T

Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Tsukuba, Ibaraki, Japan.

Gen Pharmacol. 1998 Nov;31(5):803-7. doi: 10.1016/s0306-3623(98)00085-8.

Abstract

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 microg/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.

摘要

评估了多巴胺DA1受体激动剂（-）-（S）-4-（3,4-二羟基苯基）-1,2,3,4-四氢异喹啉-7,8-二醇单盐酸盐一水合物（YM435）在犬缺血性急性肾衰竭（ARF）模型中的作用。2. 通过钳夹麻醉的单侧肾切除犬的左肾动脉1小时，随后对左肾进行再灌注来诱导ARF。3. 在肾动脉完全闭塞1小时后，开始静脉输注YM435（0.3微克/千克/分钟）或0.9%生理盐水（载体），并持续1小时。4. 在载体组中，肾缺血显著降低了肾小球滤过率、尿流和尿钠排泄。与载体组相比，YM435组的特点是肾小球滤过率、尿流和尿钠排泄有显著恢复。5. 这些结果表明，YM435可以促进缺血诱导的犬ARF模型中肾小球滤过率、尿流和尿钠排泄的恢复。YM435可能有助于缺血性ARF的肾功能保护。