Shaw S, Weidmann P, Zimmermann A
University of Bern, Medizinische Poliklinik, Switzerland.
Kidney Int. 1992 Nov;42(5):1153-9. doi: 10.1038/ki.1992.399.
The present study was undertaken to: (a) clarify the comparative renal potency of bolus injection of the natriuretic peptides urodilatin and ANF99-126 in the rat; (b) establish whether or not intravenous (i.v.) infusion of urodilatin (200 ng/min) combined with dopamine (UD) to maintain mean arterial pressure could improve GFR or renal histology in established experimental ischemic acute renal failure (ARF) induced by 30 minutes of bilateral renal artery clamping; (c) assess comparative efficacies of nitroprusside, an activator of soluble guanylate cyclase, combined with dopamine (ND) or control infusions of dopamine alone (DA), under equivalent conditions; and (d) determine effects of intra-renal arterial infusions of the stable cGMP analogue dibutyryl-cGMP immediately after renal artery clamping (RAC). After initial dose finding studies, i.v. infusion of UD 24 hours after 30 minutes of RAC improved GFR over five hours from 0.24 +/- 0.04 to 1.0 +/- 0.16 ml/min in association with a threefold rise in plasma cGMP and a 13-fold increase in urinary cGMP excretion. Plasma creatinine dropped by 41% from 230 +/- 16 to 135 +/- 18 microM/liter and was still reduced 24 hours later with values averaging 106 +/- 14 compared to 274 +/- 53 microM/liter in non-treated animals. During infusion, UV and FENa+ increased from 1.4 +/- 0.2 to 8.3 ml/min, and from 2.9 +/- 0.5 to maximum values of 15.8 +/- 2.4%. ND or DA alone were less effective, increasing GFR only to 14 and 20%, respectively, of normal values, but improvements were not sustained; in contrast to UD, ND did not alter plasma or urinary cGMP. In addition, DBcGMP was ineffective in improving GFR during early ARF. Histologically UD, but not ND, markedly reduced the incidence of granular casts, tubular desquamation and tubular necrosis in cortical areas and increased the incidence of medullary mitoses.
(a) 阐明在大鼠中推注利钠肽尿舒张素和心房钠尿肽99 - 126的相对肾脏效力；(b) 确定静脉输注尿舒张素（200 ng/分钟）联合多巴胺（UD）以维持平均动脉压是否能改善由双侧肾动脉夹闭30分钟诱导的已建立的实验性缺血性急性肾衰竭（ARF）中的肾小球滤过率（GFR）或肾脏组织学；(c) 在等效条件下评估可溶性鸟苷酸环化酶激活剂硝普钠联合多巴胺（ND）或单独多巴胺对照输注（DA）的相对疗效；以及(d) 确定肾动脉夹闭（RAC）后立即肾内动脉输注稳定的环磷酸鸟苷（cGMP）类似物二丁酰 - cGMP的效果。在初始剂量探索研究后，RAC 30分钟后24小时静脉输注UD在5小时内将GFR从0.24±0.04提高到1.0±0.16 ml/分钟，同时血浆cGMP升高三倍，尿cGMP排泄增加13倍。血浆肌酐从230±16降至135±18 μmol/升，下降了41%，24小时后仍降低，平均值为106±14，而未治疗动物为274±53 μmol/升。输注期间，UV和FENa + 分别从1.4±0.2增加到8.3 ml/分钟，从2.9±0.5增加到最大值15.8±2.4%。单独的ND或DA效果较差，仅将GFR分别提高到正常值的14%和20%，但改善未持续；与UD相反，ND未改变血浆或尿cGMP。此外，在急性肾衰竭早期，二丁酰 - cGMP在改善GFR方面无效。组织学上，UD而非ND显著降低了皮质区域颗粒管型、肾小管脱落和肾小管坏死的发生率，并增加了髓质有丝分裂的发生率。
