NDT Advance Access published online on August 25, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl444
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1 Department of Nephrology, lnstituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
* To whom correspondence should be addressed. 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- 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- Results. Systemic hypertension and marked proteinuria, increased expression of NOS-2, COX-2 and TGF- 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.
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-
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 overexpression in 5/6 nephrectomized rats
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
Laura Gabriela Sánchez-Lozada, E-mail: lgsanchezlozada{at}hotmail.com
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Abstract
1 (TGF-
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-
1, as well as the structural renal injury in rats with subtotal renal ablation (5/6 Nx).
1 gene expression was determined by real-time reverse transcription-polymerase-chain reaction. Protein expression was evaluated by western blot and ELISA (TGF-
1). Immunohistochemistry and morphometry were performed for NOS-2, microvascular thickening and fibrosis.
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.
1.
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