Nitric oxide modulates the acute increase of gastrointestinal transit induced by endotoxin in rats: a possible role for tachykinins.
Because of the evidence that endogenous nitric oxide (NO) plays an essential role in the physiological regulation of gastrointestinal motility we have investigated, by use of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), the role of endogenous NO in the acute endotoxin-induced changes of gastrointestinal transit. Pre-treatment with E. coli endotoxin (100 micrograms kg-1, i.v.) induced a significant increase in the gastrointestinal transit of a charcoal suspension in anaesthetized rats. Previous administration of the NO synthase inhibitor, L-NAME (10 mg kg-1, i.v.) significantly prevented the effects of endotoxin. L-arginine (200 mg kg-1, i.v.) and the substance P antagonist [D-Pro2, D-Trp7,9]-substance P (SPA), significantly reversed the effects of L-NAME on gastrointestinal transit in rats treated with endotoxin. Pre-treatment with dexamethasone (5 mg kg-1, s.c., twice), an inhibitor of the expression of inducible NO synthase, did not affect the increase in the gastrointestinal transit through constitutive NO synthesis. The results suggest that constitutive nitric oxide is involved in the increase of gastrointestinal transit induced by endotoxin and that the reduction in transit induced by L-NAME in endotoxin-treated rats is mediated by endogenous tachykinins.
Martínez-Cuesta
M A
MA
Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
Barrachina
M D
MD
Beltrán
B
B
Calatayud
S
S
Esplugues
J
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005772:Gastrointestinal Transit / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D004791:Enzyme Inhibitors; D015320:Tachykinins; D009569:Nitric Oxide; D013373:Substance P; C044101:endotoxin, Escherichia coli; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester