CV-11974, angiotensin II type I receptor antagonist, reduces the severity of indomethacin-induced rat enteritis.
The aim of the present study was to examine the effect of angiotensin II type I receptor antagonist, CV-11974, on indomethacin-induced small intestinal injury in rats. Single administration of indomethacin provoked severe inflammatory lesions in the small intestine. The levels of thiobarbituric acid-reactive substances (TBARS), myeloperoxidase (MPO) activities and cytokine-induced neutrophil chemoattractant-1 (CINC-1) in the intestinal mucosa significantly increased in the indomethacin-treated group compared with the sham group. In addition, the angiotensin II type I receptor was increased in the small intestine after the administration of indomethacin. The development of intestinal lesions in response to indomethacin was prevented by pretreatment with CV-11974 together with significant suppression of the increased level of TBARS, MPO activities and CINC-1. These results indicate that CV-11974 protected against the small intestinal damage elicited by indomethacin, which suggests that angiotensin II/AT1 receptor interaction is involved in the pathogenesis of the intestinal inflammation associated with oxidative stress.
Okuda
Toshimitsu
T
Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yoshida
Norimasa
N
Takagi
Tomohisa
T
Handa
Osamu
O
Kokura
Satoshi
S
Ichikawa
Hiroshi
H
Naito
Yuji
Y
Yoshikawa
Toshikazu
T
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds; D054360:Chemokine CXCL1 / Q000378:metabolism; D004751:Enteritis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007213:Indomethacin / Q000009:adverse effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000473:pathology; D008297:Male; D010437:Peptic Ulcer / Q000139:chemically induced / Q000517:prevention & control; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D017392:Thiobarbituric Acid Reactive Substances; D009195:Peroxidase; C081643:candesartan; D007213:Indomethacin