Role of NO in cyclosporin nephrotoxicity:: effects of chronic NO inhibition and NO syntheses gene expression

被引:72
作者
Bobadilla, NA
Gamba, G
Tapia, E
García-Torres, R
Bolio, A
López-Zetina, P
Herrera-Acosta, J
机构
[1] Inst Nacl Cardiol Ignacio Chavez, Dept Nephrol Ch 1, Mexico City 14080, DF, Mexico
[2] Inst Nacl Cardiol Ignacio Chavez, Dept Pathol, Mexico City 14080, DF, Mexico
[3] Inst Nacl Nutr Salvador Zubiran, Mol Physiol Unit, Dept Nephrol & Mineral Metab, Mexico City 14080, DF, Mexico
[4] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 14080, DF, Mexico
关键词
micropuncture studies; preglomerular vasoconstriction; renal histopathology; reverse transcription-polymerase chain reaction; nitric oxide;
D O I
10.1152/ajprenal.1998.274.4.F791
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The role of nitric oxide (NO) during cyclosporin renal vasoconstriction was evaluated by glomerular hemodynamic and histological changes produced by chronic NO synthesis inhibition and neuronal (nNOS), inducible (iNOS), and endothelial (eNOS) NO synthases mRNA expression in renal cortex and medulla. Uninephrectomized rats treated during 7 days with vehicle (Veh), cyclosporin A (CsA) 30 mg/kg, CsA + nitro-L-arginine methyl ester (L-NAME), and Veh + L-NAME (10 mg/dl) in the drinking water were studied. Increase in arterial pressure and afferent and efferent resistances, as well as decrease in glomerular plasma flow, ultrafiltration coefficient, and single-nephron glomerular filtration rate were significantly greater with CsA + L-NAME than with CsA alone. The increase in afferent resistance was higher with CsA + L-NAME than with Veh + L-NAME. In addition, glomerular thrombosis, proximal tubular vacuolization, and arteriolar thickening were more prominent. In renal cortex, eNOS mRNA expression exhibited a 2.7-fold increase in CsA, whereas, in medulla, nNOS and iNOS expression were lower in CsA than in Veh, while eNOS tended to increase. Our results support the hypothesis that NO synthesis is enhanced at cortical level during CsA nephrotoxicity, counterbalancing predominantly preglomerular vasoconstriction. Higher NO production could be the result of increased eNOS mRNA expression.
引用
收藏
页码:F791 / F798
页数:8
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