Skip Navigation



NDT Advance Access published online on August 25, 2006

Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl444
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
21/11/3074    most recent
gfl444v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Bautista-García, P.
Right arrow Articles by Herrera-Acosta, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bautista-García, P.
Right arrow Articles by Herrera-Acosta, J.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received June 7, 2006
Accepted June 27, 2006


Original Article

Chronic inhibition of nos-2 ameliorates renal injury, as well as COX-2 and TFG-{beta}1 overexpression in 5/6 nephrectomized rats

Pablo Bautista-García 1, Laura Gabriela Sánchez-Lozada 1 *, Magdalena Cristóbal-García 1, Edilia Tapia 1, Virgilia Soto 2, Ma. Carmen Ávila-Casado 2, Ricardo Márquez-Velasco 3, Rafael Bojalil 3, Martha Franco 1, and Jaime Herrera-Acosta 1

1 Department of Nephrology, lnstituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
2 Department of Pathology, lnstituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
3 Department of Immunology, lnstituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico

* To whom correspondence should be addressed.
Laura Gabriela Sánchez-Lozada, E-mail: lgsanchezlozada{at}hotmail.com



  Abstract

Background. Chronic renal damage is associated with inflammatory infiltration, fibrosis and vascular lesion, coupled with increased expression of cyclo-oxygenase 2 (COX-2) and transforming growth factor-{beta}1 (TGF-{beta}1). However, the role of inducible nitric oxide synthase (NOS-2) is still controversial. Thus, we studied the contribution of NOS-2 to the expression levels of COX-2 and TGF-{beta}1, as well as the structural renal injury in rats with subtotal renal ablation (5/6 Nx).

Methods. Four groups of rats were studied: sham, 5/6 Nx, 5/6 Nx + aminoguanidine (AG) and 5/6 NX + L-NIL (L-N6-iminoethyl-lysine). Systolic blood pressure (SBP), proteinuria and creatinine (Cr) clearance were measured. NOS-2, COX-2 and TGF-{beta}1 gene expression was determined by real-time reverse transcription-polymerase-chain reaction. Protein expression was evaluated by western blot and ELISA (TGF-{beta}1). Immunohistochemistry and morphometry were performed for NOS-2, microvascular thickening and fibrosis.

Results. Systemic hypertension and marked proteinuria, increased expression of NOS-2, COX-2 and TGF-{beta}1, thickening of arteriolar wall and tubulointerstitial fibrosis were produced in 5/6 Nx rats. Chronic inhibition of NOS-2 did not prevent arterial hypertension or the fall in Cr clearance, but partially reduced proteinuria. Nevertheless, AG and L-NIL preserved arteriolar morphology and the administration of both selective inhibitors of inducible NOS (AG and L-NIL) prevented NOS-2 overexpression.

Conclusion. This study shows that NOS-2 was markedly enhanced in renal tissue of 5/6 Nx rats. Moreover, treatment with AG and L-NIL prevented the morpho-functional changes induced by subtotal renal ablation, despite persistence of systemic hypertension, suggesting that high concentrations of nitric oxide produced by NOS-2 could act as a positive modulator of the proinflammatory and profibrotic pathways involved in the progression of renal disease.

Keywords: aminoguanidine and L-NIL; COX-2; 5/6 nephrectomy; NOS-2; TGF-{beta}1.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
Am. J. Physiol. Renal Physiol.Home page
E. Tapia, D. J. Sanchez-Gonzalez, O. N. Medina-Campos, V. Soto, C. Avila-Casado, C. M. Martinez-Martinez, R. J. Johnson, B. Rodriguez-Iturbe, J. Pedraza-Chaverri, M. Franco, et al.
Treatment with pyrrolidine dithiocarbamate improves proteinuria, oxidative stress, and glomerular hypertension in overload proteinuria
Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1431 - F1439.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
C. Cruz, R. Correa-Rotter, D. J. Sanchez-Gonzalez, R. Hernandez-Pando, P. D. Maldonado, C. M. Martinez-Martinez, O. N. Medina-Campos, E. Tapia, D. Aguilar, Y. I. Chirino, et al.
Renoprotective and antihypertensive effects of S-allylcysteine in 5/6 nephrectomized rats
Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1691 - F1698.
[Abstract] [Full Text] [PDF]



Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.