ROLE OF ENDOTHELIN IN CYCLOSPORINE-INDUCED GLOMERULAR DYSFUNCTION
ROLE OF ENDOTHELIN IN CYCLOSPORINE-INDUCED GLOMERULAR DYSFUNCTION
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DOI：
10.1038/ki.1990.139
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发表时间：
1990-06-01
影响因子：
19.6
通讯作者：
HOOVER, RL
中科院分区：
文献类型：
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作者：
KON, V;SUGIURA, M;HOOVER, RL
由于最近的研究表明，环孢素（CsA）破坏内皮细胞的完整性，损伤的内皮细胞释放过量的内皮素，我们研究了内皮素在急性环孢素肾毒性中的作用。在CsA （20 mg/kg静脉注射）后，兔抗猪内皮素（aE）血清连续输注于慕尼黑- wistar大鼠肾主动脉一级分支，同时用微穿刺技术评估未输注aE和同一肾脏输注aE的肾小球的血流动力学。在CsA治疗的肾脏中，未输注aE的肾小球中，单肾单位GFR （SNGFR）和肾小球血浆流速（QA）显著下降（平均分别下降42%和48%），低于基线值，这与肾小球毛细血管压力降低和传入小动脉阻力升高有关。相比之下，在同一组经CsA治疗的肾脏内输注aE的肾小球中，这种血管收缩模式明显减弱：SNGFR平均仅比基线低19%，QA值以及其他决定肾小球滤过的参数处于或接近给予CsA前的水平。另一组大鼠（N = 6）给予相同剂量的CsA，测定内皮素的循环水平。在这些CsA处理大鼠中，内皮素水平（通过放射免疫测定）升高至41.7 +-。14.7 pg/ml，与未给予CsA的相同仪器正常大鼠（N = 5）观察到的< 2 pg/ml的值一致。因此，环孢素是内皮素释放的潜在诱导剂，内皮素似乎在环孢素诱导的急性肾血管收缩和肾小球功能障碍的病理生理中起关键作用。
Since recent studies indicate that cyclosporine (CsA) disrupts endothelial integrity and that injured endothelial cells release excess endothelin, we examined endothelin''s role in acute cyclosporine nephrotoxicity. Following CsA (20 mg/kg i.v.), rabbit anti-porcine endothelin (aE) serum was continuously infused into a first order branch of the main renal artery in Munich-Wistar rats where upon the hemodynamics of glomeruli not infused with aE as well as those infused with aE within the same kidney were simultaneously assessed by micropuncture techniques. In CsA treated kidneys, in glomeruli not infused with aE, single nephron GFR (SNGFR) and glomerular plasma flow rate (QA) fell profoundly (on average by 42 and 48%, respectively) below the baseline values in association with lower glomerular capillary pressure and elevated afferent arteriolar resistance. By contrast, in glomeruli infused with aE within the same CsA treated kidneys, this vasoconstrictive pattern was markedly attenuated: SNGFR was, on average, only 19% lower than baseline and values for QA as well as other parameters determining glomerular filtration were at or near the levels observed before administration of CsA. In another group of rats (N = 6) an identical dose of CsA was given to measure the circulating level of endothelin. In these CsA treated rats, endothelin level (measured by radioimmunoassay) was elevated at 41.7 .+-. 14.7 pg/ml, contrasting the value of < 2 pg/ml uniformly observed in identically instrumented normal rats not given CsA (N = 5). Thus, cyclosporine is a potential inducer for endothelin release and endothelin appears to have a pivotal role in pathophysiology of cyclosporine-induced acute renal vasoconstriction and glomerular dysfunction.