In liver cirrhosis, elevated levels of NO and ROS (reactive oxygen species) might greatly favour the generation of peroxynitrite. Peroxynitrite is a highly reactive oxidant and it can potentially alter the vascular reactivity and the function of different organs. In the present study, we evaluated whether peroxynitrite levels are related to the progression of renal vascular and excretory dysfunction during experimental cirrhosis induced by chronic BDL (bile-duct ligation) in rats. Experiments were performed at 7, 15 and 21 days after BDL in rats and in rats 21 days post-BDL chronically treated with L-NAME (NG-nitro-L-arginine methyl ester). Sodium balance, BP (blood pressure), basal RPP (renal perfusion pressure) and the renal vascular response to PHE (phenylephrine) and ACh (acetylcholine) in isolated perfused kidneys were measured. NO levels were calculated as 24-h urinary excretion of nitrites, ROS as TBARS (thiobarbituric acid-reacting substances), and peroxynitrite formation as the renal expression of nitrotyrosine. BDL rats had progressive sodium retention, and decreased BP, RPP and renal vascular responses to PHE and ACh in the time following BDL. They also had increasing levels of NO and ROS, and renal nitrotyrosine accumulation, especially in the medulla. All of these changes were either prevented or significantly decreased by chronic L-NAME administration. In conclusion, these results suggest that the increasing levels of peroxynitrite might contribute to the altered renal vascular response and sodium retention in the development of the experimental biliary cirrhosis. Moreover, the beneficial effects of decreasing NO synthesis are, at least in part, mediated by anti-peroxinitrite-related effects.
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July 2008
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Research Article|
June 12 2008
Effects of chronic L-NAME on nitrotyrosine expression and renal vascular reactivity in rats with chronic bile-duct ligation
Antonia Alcaraz;
Antonia Alcaraz
*Department of Physiology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
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David Hernández;
David Hernández
†Department of Medicine, Regional Center for Blood Donation, University of Murcia, 30100 Murcia, Spain
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David Iyú;
David Iyú
*Department of Physiology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
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Rubén Mota;
Rubén Mota
‡Department of Biochemistry, Molecular Biology and Immunology, University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain
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Noemí M. Atucha;
Noemí M. Atucha
*Department of Physiology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
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Antonio J. Ortiz;
Antonio J. Ortiz
§Department of Dermatology, Estomatology, Radiology and Medical Physics, University of Murcia, 30100 Murcia, Spain
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Joaquín García-Estañ;
Joaquín García-Estañ
*Department of Physiology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
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María C. Ortiz
*Department of Physiology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
Correspondence: Dr María C. Ortiz (email clara@um.es).
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Publisher: Portland Press Ltd
Received:
September 05 2007
Revision Received:
December 19 2007
Accepted:
January 09 2008
Accepted Manuscript online:
January 09 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2008 Biochemical Society
2008
Clin Sci (Lond) (2008) 115 (2): 57–68.
Article history
Received:
September 05 2007
Revision Received:
December 19 2007
Accepted:
January 09 2008
Accepted Manuscript online:
January 09 2008
Citation
Antonia Alcaraz, David Hernández, David Iyú, Rubén Mota, Noemí M. Atucha, Antonio J. Ortiz, Joaquín García-Estañ, María C. Ortiz; Effects of chronic L-NAME on nitrotyrosine expression and renal vascular reactivity in rats with chronic bile-duct ligation. Clin Sci (Lond) 1 July 2008; 115 (2): 57–68. doi: https://doi.org/10.1042/CS20070312
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