Effect of intravenous L-NMMA on nitric oxide production in collagenous colitis.
BACKGROUND
Nitric oxide (NO) is greatly increased in the colon of patients with inflammatory bowel disease of different aetiology, including collagenous colitis. In man, NO can be generated from NO synthases as well as from non-enzymatic sources. The source of the NO found in luminal intestinal gas has not been exactly pinpointed. We investigated the effect of the NO synthase inhibitor L-NMMA on intestinal concentrations of NO in patients with clinically active collagenous colitis. In addition, we measured NO levels from the respiratory tract.


METHODS
Ten patients with active collagenous colitis were studied. NO levels were measured from the respiratory tract and in the rectum before and after i.v. administration of L-NMMA (7.5 mg/kg) using a chemiluminescence method.


RESULTS
Airway NO release decreased markedly, and mean arterial blood pressure increased in all patients following L-NMMA treatment. Basal rectal NO levels were high (median > 10000 ppb) and decreased markedly in 5 patients after L-NMMA. In contrast, NO levels remained completely unchanged or even increased in the other 5 patients.


CONCLUSIONS
Rectal levels of NO are greatly increased in patients with symptomatic collagenous colitis. Intravenous administration of an NO synthase inhibitor reduced rectal NO only in half of the patients despite clear evidence of effective systemic NO synthase inhibition. This could indicate alternative NOS-independent sources of intestinal NO in this disease.
Dept. of Physiology and Pharmacology, Division of Pharmacology, Karolinska Institute, Stockholm, Sweden. Claudia.Reinders@fyfa.ki.se
C I
CI
Reinders
P M
PM
Hellström
J
J
Björk
E
E
Weitzberg
J O
JO
Lundberg
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003092:Colitis / Q000378:metabolism*; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D012137:Respiratory System / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000008:administration & dosage*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003094:Collagen