Suppression of dextran sulfate sodium-induced colitis in kininogen-deficient rats and non-peptide B2 receptor antagonist-treated rats.
Various proinflammatory mediators are believed to be involved in the processes and symptoms of ulcerative colitis (UC). To determine whether endogenous kinin enhances the severity of UC, we induced experimental colitis (EC) in kininogen-deficient mutant rats and tested the effect of a non-peptide B2 receptor antagonist. EC was induced in male kininogen-deficient Brown Norway-Katholiek rats (BN-Ka) and normal Brown Norway-Kitasato rats (BN-Ki) with 5% dextran sulfate sodium (DSS). Sprague-Dawley rats (SD) were also used. Colon length, body weight and hematocrit were determined for 7 days. Effects of FR173657, an orally active B2 antagonist, were tested. The colon length was shortened in BN-Ki with DSS treatment, but not in BN-Ka, and the difference between their lengths was significant. The hematocrit value was also reduced in BN-Ki, and the difference in hematocrit between BN-Ki and BN-Ka was significant. In SD, shortening of the colon and reduction in hematocrit were also observable, and both were blunted by FR173657. The survival rate in SD given DSS for 7 days was 68%, but FR173657 treatment restored it significantly to 100%. These results suggest that the endogenous kinins generated from the kallikrein-kinin system have a significant role in the development of EC.
Kamat
Kazuhisa
K
Department of Internal Medicine, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan.
Hayashi
Izumi
I
Mizuguchi
Yoshito
Y
Arai
Katsuharu
K
Saeki
Takeo
T
Ohno
Takashi
T
Saigenji
Katsunori
K
Majima
Masataka
M
D000818:Animals; D065168:Bradykinin Receptor Antagonists; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity*; D007704:Kininogens / Q000172:deficiency* / Q000235:genetics; D007705:Kinins / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011914:Rats, Inbred BN; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism
D065168:Bradykinin Receptor Antagonists; C105311:FR 173657; D007704:Kininogens; D007705:Kinins; D011804:Quinolines; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D016264:Dextran Sulfate