Comparative study of the effects of nitric oxide synthase and cyclo-oxygenase inhibition on duodenal functions in rats anaesthetized with inactin, urethane or alpha-chloralose.
This study was undertaken to investigate the effects of a cyclo-oxygenase and a nitric oxide synthase (NOS) inhibitor on duodenal mucosal alkaline secretion (DMAS), motility and mucosal permeability in inactin-, urethane- and alpha-chloralose anaesthetized rats. Proximal duodenum was perfused with a 150 mM NaCl solution and DMAS was determined by back titration. Mucosal permeability was assessed by measuring blood to lumen clearance of 51Cr-EDTA and duodenal motility by measuring intraluminal pressure. Mean arterial blood pressure and mucosal permeability were significantly lower in urethane- than in inactin- or alpha-chloralose anaesthetized rats (urethane: 90 +/- 2 mm Hg and 0.15 +/- 0.02 mL min-1 100 g-1; inactin: 112 +/- 5 mm Hg and 0.62 +/- 0.15 mL min-1 100 g-1; alpha-chloralose: 111 +/- 4 mm Hg and 0.61 +/- 0.06 mL min-1 100 g-1, respectively). Basal (pre-drug) DMAS was significantly lower in urethane rats (6.2 +/- 1.0 mumol cm-1 h-1) than in alpha-chloralose (9.3 +/- 1.2 mumol cm-1 h-1), but not different from that in inactin-anaesthetized rats (7.5 +/- 0.8 mumol cm-1 h-1). No or very few spontaneous duodenal contractions occurred under the control (pre-drug) conditions in any group. All animals responded to the cyclo-oxygenase inhibitor indomethacin or the NOS inhibitor N-nitro-L-arginine-methyl-ester (L-NAME) with induction of duodenal motility and an increase in DMAS. The effect of indomethacin or L-NAME on mucosal permeability was similar in all anaesthetic groups except that L-NAME induced a transient increase in the inactin and alpha-chloralose groups but a sustained increase in urethane-anaesthetized animals. It is concluded that inactin- and alpha-chloralose anaesthetized rats do not differ regarding the studied basal values. Urethane-anaesthetized animals differed from rats given the other two anaesthetics in that basal mucosal permeability and mean arterial blood pressure were lower. Endogenous prostaglandins and NO contribute to the postoperative ileus and the low rate of DMAS also in urethane- and alpha-chloralose.
Sababi
M
M
Department of Physiology and Medical Biophysics, Uppsala University, Sweden.
Nylander
O
O
D000768:Anesthesia, General; D018686:Anesthetics, Intravenous; D000818:Animals; D002698:Chloralose; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013874:Thiopental / Q000031:analogs & derivatives; D014520:Urethane
D018686:Anesthetics, Intravenous; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D002698:Chloralose; C004316:thiobutabarbital; D014520:Urethane; D019001:Nitric Oxide Synthase; D013874:Thiopental; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin