An angiotensin II receptor antagonist reduces inflammatory parameters in two models of colitis

Little is known about the effects of the pro-inflammatory hormone Angiotensin II (Ang II) in inflammatory bowel disease. The aim of this study was to evaluate the effect of valsartan (Diovan), an Ang II receptor antagonist, in two models of colitis. Methods: Colitis was induced in Sprague-Dawley rats by administration of trinitrobenzene sulfonic acid (TNBS; 30 mg in 50% ETOH ic) or 5% Dextran Sulphate Sodium (DSS) in drinking water ad libitum for 5days. Valsartan was administered orally in drinking water (160 mg/L) during thirty days prior to the induction of the colitis, and for 5days after. All animals were evaluated for weight change, diarrhea, myeloperoxidase activity, macroscopic and microscopic damage. Cytokine levels in the colon were measured by ELISA, real-time RT-PCR and immunohistochemistry. Results: In the TNBS model, valsartan reduced the macroscopic damage score, significantly decreased the microscopic damage (p < 0.01), and accelerated weight gain after colitis. In the DSS-colitis model, valsartan-treated animals had less diarrhea and microscopic damage. Valsartan reduced the protein levels of TGF beta (p < 0.05), and IL-18 in the TNBS model, and led to over expression of IL-10 mRNA in the DSS model. Conclusion: These data demonstrate a possible anti-inflammatory effect for valsartan in colitis. (C) 2007 Elsevier B.V. All rights reserved.