The roles of endothelin and growth factors in ischemic acute renal failure.

探讨内皮素和血栓素A2在大鼠缺血性急性肾功能衰竭中的作用。左肾动脉闭塞60分钟导致左肾菊糖清除率（Cin）降低，组织学改变包括肾小管坏死和铸型形成。在缺血后48小时，先行右肾切除术可减轻肾小管坏死和肾素的减少。右肾切除术的有益效果与肾内皮素和血栓素B2含量升高的衰减有关。单克隆内皮素抗体（AwETN40）或内皮素A受体拮抗剂（FR 139317）在右肾切除组和假肾切除组均未能减轻Cin的下降和组织学变化。本实验使用的剂量足以抑制内皮素1.2 nmol/kg的高血压作用。相反，血栓素A2合成抑制剂（oky046）可以减轻假性肾切除术大鼠缺血引起的尿量、肾血流量和肾素的减少。这些结果表明，血栓素A2的肾内作用而非内皮素的肾内作用可能在右肾切除术诱导的缺血性急性肾功能衰竭的衰减中起关键作用。

The roles of endothelin and thromboxane A2 in ischemic acute renal failure were evaluated in rats. A 60 min left renal artery occlusion induced a decrease in inulin clearance(Cin) in left kidney and histological changes including tubular necrosis and cast formation. Antecedent nephrectomy of right kidney attenuates the decrease in Cin and tubular necrosis at 48 hours after ischemia. The beneficial effects of right nephrectomy was associated with the attenuation of the increases in renal endothelin and thromboxane B2 contents. The treatment with monoclonal endothelin antibody(AwETN40) or endothelin A receptor antagonist(FR 139317) failed to attenuate the decline of Cin and histological changes in both right nephrectomized and sham nephrectomized groups. The doses that we used in this experiment was enough to inhibit the hypertensive effects of 1.2 nmol/kg of endothelin. In contrast, the inhibitor of thromboxane A2 synthesis(OKY 046) attenuated the ischemia-induced decreases in urine output, renal blood flow and Cin in sham nephrectomized rats. These results suggest that intrarenal action of thromboxane A2 but not of endothelin may play a key role in right nephrectomy-induced attenuation of ischemic acute renal failure.