| Title | Differential salutary effects of nonselective and selective COX-2 inhibitors in postoperative ileus in rats. | | Author(s) | Korolkiewicz RP, Ujda M, Dabkowski J, Ruczyński J, Rekowski P, Petrusewicz J | | Institution | Department of Pharmacology, Medical University of Gdańsk, Poland. rokor@amedec.amg.gda.pl | | Source | J Surg Res 2003 Feb; 109(2):161-9. | | MeSH | Animals
Arginine
Comparative Study
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Gastrointestinal Motility
Intestinal Pseudo-Obstruction
Intestines
Isoenzymes
Laparotomy
Lysine
Male
Models, Animal
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Postoperative Complications
Prostaglandin-Endoperoxide Synthases
Prostaglandins
Rats
Rats, Wistar
Research Support, Non-U.S. Gov't
| | Abstract | BACKGROUND: Postoperative ileus (PI) is a common surgical complication, the treatment of which consists of supportive measures.
AIM: The effects of several cyclooxygenase (COX) inhibitors and their interaction with L-arginine/nitric oxide synthase (NOS) pathway were tested in a rat PI model.
METHODS: Intestinal transit was measured as Evans blue migration after skin incision, laparotomy, or laparotomy followed by evisceration and gut handling.
RESULTS: In contrast to a selective inducible NOS (iNOS) blocker, L-N(6)-(1-iminoethyl)lysine hydrochloride (L-NIL), N(omega)-nitro-L-arginine methyl ester (L-NAME) reversed the additional inhibitory effects of gut manipulation after laparotomy on the gastrointestinal transit (GI) in a dose-dependent, L-arginine-sensitive manner. Laparotomy and manipulations of small intestine increased blood plasma nitrites and nitrates level (NOx), an effect preventable by L-NAME. Indomethacin, resveratrol (selective COX-1 blocker), and COX-2 antagonists, nimesulide, NS-398, DuP-697, and L-752860, attenuated the additional inhibitory effects of gut manipulation following laparotomy in a dose-dependent manner. In contrast, only nimesulide, NS-398, DuP-697, and L-752860 partly, but significantly, reversed the effects of laparotomy on the intestinal transit. Administration of L-NAME subsequent to COX inhibitors abolished the salutary effects of the latter, implying that at least the synthesis of either NO or prostanoids must remain unaffected to enable a return of GI transit during the postoperative period.
CONCLUSION: In addition to NO synthesized by constitutive NOS (cNOS), prostaglandins produced by both COX-1 and COX-2 participate in the pathogenesis of PI, albeit in different pathological mechanisms. Thus laparotomy stimulated COX-2 activity, whereas gut manipulation led to an excessive cNOS activity and prostaglandin synthesis by COX-1. | | Language | eng | | Pub Type(s) | Evaluation Studies
Journal Article
| | PubMed ID | 12643859 |
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