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 i.c.) or 5% Dextran Sulphate Sodium (DSS) in drinking water ad libitum for 5 days. Valsartan was administered orally in drinking water (160 mg/L) during thirty days prior to the induction of the colitis, and for 5 days 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 TGFbeta (p<0.05), and IL-18 in the TNBS model, and led to over expression of IL-10 mRNA in the DSS model.


CONCLUSIONS
These data demonstrate a possible anti-inflammatory effect for valsartan in colitis.
Santiago
Olga I
OI
Department of Physiology and Pharmacology, Ponce School of Medicine, Ponce, 00732, Puerto Rico.
Rivera
Edelmarie
E
Ferder
Leon
L
Appleyard
Caroline B
CB
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D016207:Cytokines; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine