Nitric oxide prevents rat duodenal contractions induced by potentially noxious agents.
After abdominal surgery, luminal HCl fails to induce duodenal contractions in anaesthetized rats. Elevated tissue levels of nitric oxide (NO) and prostaglandins possibly contribute to this observation. The aim of this study was to compare the effects of luminal capsaicin (1.2 mg mL-1), ethanol (15%) and high partial pressure of CO2 (>250 mmHg) with those of HCl (10 mM) in anaesthetized rats. Motility (intraluminal pressure), mucosal permeability [blood-to-lumen clearance of 51Cr-EDTA (51Chromium-labelled ethylenediaminetetraacetate)] and duodenal mucosal bicarbonate secretion (DMBS) were recorded. Three groups of animals were studied: (1) controls, (2) pretreatment with the NO synthase inhibitor N-nitro-L-arginine-methyl-ester (L-NAME) and (3) pretreatment with the cyclo-oxygenase inhibitor indomethacin. Neither capsaicin, ethanol, CO2 nor HCl induced duodenal contractions or affected DMBS in control rats. However, L-NAME induced duodenal contractions that were augmented by capsaicin, ethanol and HCl, but not by CO2. Indomethacin also induced contractions that were reversibly diminished by capsaicin and HCl, but not by ethanol or CO2. Significant increases in mucosal permeability occurred during ethanol perfusion in indomethacin- and L-NAME pretreated rats. In conclusion, NO probably plays a key role in preventing duodenal contractions in response to luminally HCl, capsaicin and ethanol. The HCl-induced effect on motility appears to be independent of CO2 and is not caused by alteration in mucosal integrity.
Hellgren
S
S
Department of Physiology, Biomedical Centre, Uppsala University, Uppsala, Sweden.
Flemström
G
G
Nylander
O
O
D000818:Animals; D001120:Arginine / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D002211:Capsaicin / Q000008:administration & dosage; D002245:Carbon Dioxide / Q000008:administration & dosage; D002860:Chromium Radioisotopes; D003433:Crosses, Genetic; D004386:Duodenum / Q000187:drug effects*; D004492:Edetic Acid / Q000493:pharmacokinetics; D000431:Ethanol / Q000008:administration & dosage; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006851:Hydrochloric Acid / Q000008:administration & dosage; D007213:Indomethacin / Q000008:administration & dosage; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007441:Intubation, Gastrointestinal; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains
D001639:Bicarbonates; D002860:Chromium Radioisotopes; D002245:Carbon Dioxide; D009569:Nitric Oxide; D000431:Ethanol; D001120:Arginine; D004492:Edetic Acid; D006851:Hydrochloric Acid; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin