Products of cyclooxygenase-2 depress duodenal function in rats subjected to abdominal surgery.
OBJECTIVE
Abdominal surgery evokes powerful biological responses that affect gastrointestinal functions. Here we investigate the role of the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoforms in post-operative duodenal ileus.


METHODS
Proximal duodenum of anesthetized rats was perfused in situ with isotonic or hypotonic (50 mM) NaCl. Mucosal bicarbonate secretion, motility, mucosal permeability and effluent osmolality were determined in the absence and presence of different COX inhibitors.


RESULTS
The majority of control animals had no or few duodenal contractions and bicarbonate secretion averaged 10.9 +/- 1.4 micromol cm(-1) h(-1). These 'paralytic' controls responded to hypotonic NaCl with a small increase in mucosal permeability. In control animals exhibiting spontaneous duodenal contractions, the bicarbonate secretion was 50% higher and the hypotonicity-induced net increase in mucosal permeability sevenfold higher than in 'paralytic' controls. Treatment with the selective COX-2 inhibitors rofecoxib or parecoxib induced duodenal motility, increased bicarbonate secretion and potentiated the hypotonicity-induced increase in mucosal permeability. COX-2-inhibited animals had a twofold greater capacity to adjust luminal osmolality than 'paralytic' controls. The selective COX-1 inhibitor SC-560 only transiently stimulated motility and bicarbonate secretion and the hypotonicity-induced increase in mucosal permeability was smaller than in COX-2-inhibited animals.


CONCLUSIONS
Abdominal surgery increases the synthesis of prostanoids, particularly via the COX-2 isoform. This compromises the ability of the duodenum to contract and to secrete HCO and to adjust luminal osmolality possibly via altered mucosal permeability. It is proposed that studies of gastrointestinal functions in animals subjected to abdominal surgery should include animals pre-treated with a COX-2 inhibitor.
Pihl
L
L
Department of Neuroscience, Division of Physiology, Biomedical Center, Uppsala University, Uppsala, Sweden.
Nylander
O
O
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D007813:Laparotomy / Q000009:adverse effects*; D008297:Male; D009994:Osmolar Concentration; D010477:Perfusion; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D012965:Sodium Chloride / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology
D001639:Bicarbonates; D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; D007783:Lactones; D011720:Pyrazoles; C115461:SC 560; D013450:Sulfones; C116926:rofecoxib; D012965:Sodium Chloride; C409945:parecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2