Is nitric oxide and heparin treatment justified in inflammatory bowel disease? An experimental study.
Microcirculatory disturbances of the colon may contribute to the pathogenesis of inflammatory bowel disease. The aim of the study was to investigate the alterations of rectal blood perfusion in experimental colitis with reference to nitric oxide and heparin treatment. The study was carried out on 36 rats, divided into six groups: group I, control; group II, control + NG-nitro-L-arginine (L-NNA); group III, colitis without treatment; group IV, colitis + L-arginine; group V, colitis + L-NNA; group VI, colitis + heparin treatment. Experimental colitis was induced by 4% acetic acid enema, and 48 h after the enema, besides the measurement of rectal capillary blood flow by means of laser Doppler flowmetry, the serum interleukin-6 (IL-6) level and histopathological alterations within the rectal mucosa were examined. Experimental colitis resulted in a drop in rectal wall perfusion. L-Arginine and heparin treatment improved the microcirculatory values. The highest IL-6 level and the most advanced histopathological alterations were observed in the rats treated with L-NNA. L-Arginine treatment had no influence on IL-6 concentration, however it aggravated the inflammatory changes within the rectal mucosa. Heparin administration reduced the IL-6 values and also had a positive impact on the microscopic alterations within the rectal wall. It is concluded that heparin treatment has a beneficial effect on the microcirculatory disturbances and inflammatory changes observed in experimental colitis. The inhibition of nitric oxide-synthase aggravated the course of experimental colitis. L-Arginine administration improves the rectal blood flow but aggravates the histopathological alterations within the rectal wall.
Dobosz
M
M
Second Department of Surgery, Medical University of Gdańsk, Poland.
Mionskowska
L
L
Dobrowolski
S
S
Dymecki
D
D
Makarewicz
W
W
Hrabowska
M
M
Wajda
Z
Z
D019342:Acetic Acid; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002196:Capillaries; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006493:Heparin / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000098:blood supply
D004791:Enzyme Inhibitors; D015850:Interleukin-6; D019335:Nitroarginine; D009569:Nitric Oxide; D006493:Heparin; D001120:Arginine; D019001:Nitric Oxide Synthase; D019342:Acetic Acid