Kidney damage after renal ablation is worsened in endothelial nitric oxide synthase (−/−) mice and improved by combined administration of L‐arginine and antioxidants

Nephrology - Tập 13 Số 3 - Trang 218-227 - 2008
Mónica Mendoza-Rodríguez1, Carlos Castillo‐Henkel1, Roberto Medina‐Santillán1, R. Luna1, Hilda Vargas Robles2, Eunice Romo2, Amelia Rı́os3, Bruno Escalante3,2
1Escuela Superior de Medicina IPN,
2Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), México City,
3CINVESTAV Monterrey, Monterrey, NL, Mexico

Tóm tắt

SUMMARY:Aim  Reduction in nitric oxide (NO) levels during kidney failure has been related to the reaction of NO with superoxide anions to yield peroxynitrite which possesses the biological activity responsible for renal damage. However, stimulation of the NO pathway ameliorates the progression of kidney failure. Thus, it is unclear whether NO prevents or acts as the compound responsible for the cytotoxicity observed during kidney failure.Methods  We evaluated the development of kidney failure in animals that were wild type and deficient in endothelial NO synthase (eNOS (−/−)) and tested the effects of an antioxidant treatment and NO precursors on the generation of superoxide anion and kidney failure parameters.Results  In wild‐type mice, five‐sixths nephrectomy increased proteinuria from 3.0 ± 0.35 to 14.5 ± 0.76 mg protein/24 h (P < 0.05), blood pressure from 83.1 ± 1.8 to 126.6 ± 1.7 mmHg (P < 0.05), and superoxide production from 1.4 ± 0.6% to 74.3 ± 0.8% (P < 0.05). The effects of five‐sixths nephrectomy on the eNOS (−/−) mice were greater compared with wild‐type mice. Proteinuria increased from 6.7 ± 0.5 to 22.7 ± 2.0 mg protein/24 h (P < 0.05), blood pressure increased from 93.3 ± 0.9 to 151.2 ± 3.4 mmHg (P < 0.05), and superoxide production increased from 12.9 ± 0.5% to 99.8 ± 1.3% (P < 0.05). The nitrotyrosine levels were lower in eNOS (−/−) mice as compared to wild‐type mice. A combination of L‐arginine and antioxidant treatment ameliorated renal damage. The effect was improved in wild‐type animals.Conclusion  Our data support the relevance of NO as an antagonist to superoxide in renal tissues and suggest that the loss of this mechanism promotes the progression of kidney failure.

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Nephrology

Tập 13 Số 3

218-227

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