Downregulation of nNOS and synthesis of PGs associated with endotoxin-induced delay in gastric emptying

Am J Physiol Gastrointest Liver Physiol. 2002 Dec;283(6):G1360-7. doi: 10.1152/ajpgi.00168.2002.


A single intraperitoneal injection of endotoxin (40 microg/kg) significantly delayed gastric emptying of a solid nutrient meal. Blockade of nitric oxide synthase (NOS) with 30 mg/kg ip N(G)-nitro-L-arginine methyl ester or 20 mg/kg ip 7-nitroindazole [neuronal NOS (nNOS) inhibitor] significantly delayed gastric emptying in control animals but failed to modify gastric emptying in endotoxin-treated rats. Administration of 2.5, 5, and 10 mg/kg ip N(6)-iminoethyl-L-lysine [inducible NOS (iNOS) inhibitor] had no effect in either experimental group. Indomethacin (5 mg/kg sc), NS-398 (cyclooxygenase-2 inhibitor; 10 mg/kg ip), and dexamethasone (10 mg/kg sc) but not quinacrine (20 mg/kg ip) significantly prevented delay in gastric emptying induced by endotoxin but failed to modify gastric emptying in vehicle-treated animals. Ca(2+)-dependent NOS activity in the antrum pylorus of the stomach was diminished by endotoxin, whereas Ca(2+)-independent NOS activity was not changed. In addition, decreased nNOS mRNA and protein were observed in the antrum pylorus of endotoxin-treated rats. Our results suggest that downregulation of nNOS in the antrum pylorus of the stomach and synthesis of prostaglandins mediate the delay in gastric emptying of a solid nutrient meal induced by endotoxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / antagonists & inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Endotoxins / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Food
  • Gastric Emptying / drug effects*
  • Indazoles / pharmacology
  • Indomethacin / pharmacology
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / physiology
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitrobenzenes / pharmacology
  • Phospholipases A / antagonists & inhibitors
  • Prostaglandins / biosynthesis*
  • Pyloric Antrum / enzymology
  • Quinacrine / pharmacology
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonamides / pharmacology


  • Cyclooxygenase Inhibitors
  • Endotoxins
  • Enzyme Inhibitors
  • Indazoles
  • Nitrobenzenes
  • Prostaglandins
  • RNA, Messenger
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Arachidonic Acid
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nos1 protein, rat
  • Nos2 protein, rat
  • Phospholipases A
  • Quinacrine
  • 7-nitroindazole
  • NG-Nitroarginine Methyl Ester
  • Indomethacin