INCREASED RENAL ENDOTHELIN PRODUCTION IN RATS WITH REDUCED RENAL MASS

INCREASED RENAL ENDOTHELIN PRODUCTION IN RATS WITH REDUCED RENAL MASS
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DOI:
10.1152/ajprenal.1991.260.3.f331
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发表时间:
1991-03-01
影响因子:
--
通讯作者:
REMUZZI, G
REMUZZI, G
中科院分区:
其他
文献类型:
--
作者:
BENIGNI, A;PERICO, N;REMUZZI, G

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以肾小球血流动力学改变和毛细血管血栓形成为主要特征的进展性肾病模型大鼠肾肿块消融术后和假手术组大鼠肾组织内皮素(ET)的产生进行了观察。凝血酶刺激肾质量减轻的大鼠肾皮质组织,术后45天而不是7天,比假手术动物产生更多的ET(P&lt;0.01)。与未受刺激的肾小球相比,暴露于残肾而非假肾的分离肾小球的凝血酶也显著增加ET的产生(P&lt;0.01)。45天时,与假手术组相比,肾切除组大鼠血浆ET水平明显降低,尿液ET排泄率显著升高(P<0.01)。正常大鼠和肾切除动物静脉注射I-125-ET 50min后,尿中放射性分别低于输注总量的0.3%和0.03%。这些结果表明,肾质量减轻的大鼠,凝血酶刺激的肾皮质组织产生的ET增加。在该模型中,尽管血浆ET水平正常或低正常,尿中肽的排泄量仍显著增加。添加到循环中的外源性标记的ET不会被肾脏排泄,这表明尿排泄率的增加反映了残留肾脏的大鼠肾脏产生的多肽增加。
Renal endothelin (ET) production was investigated in rats after renal mass ablation, a model of progressive renal disease characterized by glomerular hemodynamic alterations and capillary thrombosis, and in sham-operated animals. Thrombin stimulation of renal cortical tissue from rats with renal mass reduction, 45 but not 7 days after surgery, generated significantly (P < 0.01) more ET than tissue from sham-operated animals. Exposure to thrombin of isolated glomeruli from remnant but not sham kidneys also significantly (P < 0.01) increased ET production compared with unstimulated glomeruli. At day 45, in rats with renal mass ablation ET plasma levels were numerically lower, whereas urinary excretion rate of ET was significantly (P < 0.01) increased compared with sham-operated animals. After a 50-min intravenous infusion of I-125-ET to normal rats and animals with renal mass ablation, less than 0.3% and 0.03%, respectively, of total infused radioactivity was recovered in urine. These results indicate that thrombin-stimulated ET production by renal cortical tissues is increased in rats with renal mass reduction. Despite normal or low-normal plasma ET levels, urinary excretion of the peptide is markedly increased in this model. The exogenously labeled ET added to circulation is not excreted by the kidney, suggesting that enhanced urinary excretion rate would reflect an increased renal production of the peptide in rats with remnant kidney.