Differential effect of indomethacin and ketorolac on postoperative ileus in rats.
The effect of two prostaglandin biosynthesis inhibitors and their interaction with the L-arginine/nitric oxide (NO) pathway was investigated in a rat model of experimental ileus. The gastrointestinal transit was measured as the migration of Evans blue after three different operations. Indomethacin completely reversed the additional inhibition of the transit induced by mechanical stimulation of the gut. Ketorolac completely reversed the inhibition of the transit induced by the laparotomy, but had no additional effect on the inhibition induced by mechanical stimulation of the gut. Administration of indomethacin plus L-nitroarginine or L-arginine could not enhance or prevent the effect of indomethacin alone. Administration of ketorolac and L-nitroarginine completely reversed the transit after the laparotomy plus manipulation whereas ketorolac plus L-arginine had no additional effect as compared to ketorolac alone. From these findings we conclude that in addition to NO, prostaglandins are involved in the pathogenesis of postoperative ileus in the rat. However, indomethacin and ketorolac differentially affect postoperative ileus suggesting that prostaglandins are involved in different pathogenic mechanisms leading to postoperative ileus.
De Winter
B Y
BY
Division of Gastroenterology and Pharmacology, Faculty of Medicine, University of Antwerp, Antwerp-Wilrijk, Belgium.
Boeckxstaens
G E
GE
De Man
J G
JG
Moreels
T G
TG
Herman
A G
AG
Pelckmans
P A
PA
D000818:Animals; D004195:Disease Models, Animal; D007213:Indomethacin / Q000627:therapeutic use*; D007415:Intestinal Obstruction / Q000188:drug therapy*; D020910:Ketorolac; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D011183:Postoperative Complications; D011448:Prostaglandin Antagonists / Q000627:therapeutic use*; D051381:Rats; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D011448:Prostaglandin Antagonists; D019335:Nitroarginine; D009569:Nitric Oxide; D014046:Tolmetin; D007213:Indomethacin; D020910:Ketorolac