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

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 283; no. 6; pp. G1360 - G1367
• Main Authors: Calatayud, Sara, García-Zaragozá, Eugenia, Hernández, Carlos, Quintana, Elsa, Felipo, Vicente, Esplugues, Juan Vicente, Barrachina, María Dolores
• Format: Journal Article
• Language: English
• Published: United States 01.12.2002
• Subjects: 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; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Sulfonamides - pharmacology
• ISSN: 0193-1857; 1522-1547
• 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.