Effects of nitric oxide synthase inhibition on the pathophysiology observed in a model of chronic granulomatous colitis.
The objective of this study was to assess the role that nitric oxide (NO) may play in mediating the colonic inflammation observed in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS). The NOS inhibitors NG-nitro-L-arginine methyl ester (L-NAME; 15 mumol/kg/day) and aminoguanidine (AG; 15 mumol/kg/day) were administered to rats in their drinking water, beginning 3 days before the induction of colitis and continuing for the entire 3-week period. We found that chronic NOS inhibition by L-NAME or AG significantly attenuated the peptidoglycan/polysacchride (PG/PS)-induced increases in macroscopic colonic inflammation scores and colonic MPO activity. Only AG, and not L-NAME, attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen inflammation, whereas neither drug significantly attenuated the PG/PS-induced liver inflammation. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG was found to attenuate these values significantly (38 +/- 3 vs. 83 +/- 8 microM, respectively; P < .05). Finally, administration of L-NAME, but not of AG, significantly increased mean arterial pressure from 83 mm Hg in colitic animals to 105 mm Hg in the PG/PS+L-NAME-treated animals (P < .05). We conclude that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.
Grisham
M B
MB
Department of Physiology, Louisiana State University Medical Center, Shreveport.
Specian
R D
RD
Zimmerman
T E
TE
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D003424:Crohn Disease / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D006146:Guanidines; D009569:Nitric Oxide; D001120:Arginine; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester