Stimulation by nitric oxide synthase inhibitors of gastric and duodenal HCO3- secretion in rats.
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.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Yamashina, Japan.
Ohuchi
T
T
Miyake
H
H
Okabe
S
S
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002799:Cholinergic Fibers / Q000502:physiology; D004386:Duodenum / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D014630:Vagus Nerve / Q000502:physiology
D001639:Bicarbonates; D016232:Endothelins; D011453:Prostaglandins; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester