Stimulation by nitric oxide synthase inhibitors of gastric and duodenal HCO3- secretion in rats

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 266; no. 3; pp. 1512 - 1519
• Main Authors: TAKEUCHI, K, OHUCHI, T, MIYAKE, H, OKABE, S
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.09.1993
• Subjects: Amino Acid Oxidoreductases - antagonists & inhibitors; Animals; Arginine - analogs & derivatives; Arginine - pharmacology; Bicarbonates - metabolism; Biological and medical sciences; Capillary Permeability - drug effects; Cholinergic Fibers - physiology; Digestive system; Duodenum - blood supply; Duodenum - drug effects; Duodenum - secretion; Endothelins - pharmacology; Gastric Mucosa - blood supply; Gastric Mucosa - drug effects; Gastric Mucosa - secretion; Intestinal Mucosa - drug effects; Intestinal Mucosa - secretion; Male; Medical sciences; NG-Nitroarginine Methyl Ester; Nitric Oxide - metabolism; Nitric Oxide Synthase; Nitroprusside - pharmacology; Pharmacology. Drug treatments; Prostaglandins - physiology; Rats; Rats, Sprague-Dawley; Stimulation, Chemical; Vagus Nerve - physiology; Stomach; Intravenous administration; Duodenum; Prostaglandin; Rat; Enzyme; Digestive system; Arachidonic acid derivatives; Rodentia; Enzyme inhibitor; Biosynthesis; Hydrogencarbonates; α-Aminoacid; Vertebrata; Gastroduodenal; Mammalia; Animal; Nitrogen monoxide; Cholinergic innervation; Vagus nerve; Exocrine secretion
• ISSN: 0022-3565; 1521-0103

The role of nitric oxide (NO) in the regulation of gastroduodenal HCO3- secretion was investigated in anesthetized rats using the NO biosynthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME). HCO3- secretion was measured at pH 7.0 using a pH-stat method in the chambered stomach in the presence of omeprazole or in the proximal duodenum. Intravenous administration of L-NAME (1-5 mg/kg) increased HCO3- secretion in a dose-dependent manner in both the stomach and duodenum, with a concomitant elevation of arterial blood pressure. The stimulatory effect of L-NAME on HCO3- secretion was mimicked by another NO synthase inhibitor, NG-monomethyl-L-arginine (50 mg/kg), but not by the enantiomer NG-nitro-D-arginine methyl ester, and was significantly antagonized by concurrent administration of L-arginine, but not D-arginine, at 200 mg/kg. The exogenous NO donor nitroprusside (4 mg/kg) by itself decreased the rate of HCO3- secretion and significantly antagonized the HCO3- stimulatory action of L-NAME. Furthermore, the increased HCO3- secretion caused by L-NAME was significantly attenuated by prior administration of atropine (1 mg/kg, s.c.) or indomethacin (5 mg/kg, s.c.) and by bilateral vagotomy but was not influenced by sensory deafferentation after capsaicin pretreatment, though none of the treatments had any effect on the changes in blood pressure induced by L-NAME. These results suggest that L-NAME stimulates HCO3- secretion in the gastroduodenal mucosa. This action is associated with the inhibition of NO biosynthesis and may be partly dependent on vagal-cholinergic innervation and mediated by endogenous prostaglandins.