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。左肾动脉阻断60min后，左肾菊糖清除率(Cin)下降，肾组织学改变包括肾小管坏死和管型形成。预先切除右肾可减轻缺血后48小时Cin的减少和肾小管的坏死。右肾切除的有益作用与减轻肾组织内皮素和血栓素B_2含量的升高有关。单抗(AwETN40)或内皮素A受体拮抗剂(FR 139317)治疗均不能缓解右肾切除组和假切除组Cin的下降和组织学改变。我们在本实验中使用的剂量足以抑制1.2nmol/kg内皮素的高血压效应。相反，血栓烷A2合成抑制剂(OKY 046)可减轻缺血引起的假肾切除大鼠的尿量、肾血流量和Cin的减少。这些结果提示，血栓素A2的肾内作用可能在右肾切除所致的缺血性急性肾功能衰竭的减轻中起关键作用，而不是内皮素。

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.