The mechanism underlying stimulation of gastric HCO3- secretion by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester in rats.
We investigated the mechanism underlying stimulation of gastric HCO3- secretion by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in anaesthetized rats. A rat stomach was mounted in an ex vivo chamber, superfused with saline, and HCO3- secretion was measured in the absence of acid secretion (omeprazole pretreatment). Intravenous administration of L-NAME (1-5 mg/kg) increased gastric HCO3- secretion dose dependently with concomitant rise in arterial blood pressure and decrease in heart rate, and these effects were all antagonized by simultaneous administration of L-arginine (200 mg/kg). Vagotomy did not affect the increased blood pressure response but significantly inhibited the decrease in heart rate and increase of HCO3- secretion caused by L-NAME. The HCO3- stimulatory action of L-NAME was also inhibited by pretreatment with either yohimbine (5 mg/kg s.c.) or prazosin (0.5 mg/kg s.c.). These agents alone caused a decrease in blood pressure, and reduced the magnitude of blood pressure response caused by L-NAME, leading to inhibition of heart rate changes. When the change in HCO3- output induced by L-NAME was plotted against the change in blood pressure (from basal values) under various conditions, a significant relationship was found between these two parameters. These results suggest that L-NAME stimulates gastric HCO3- secretion in association with the inhibition of endogenous NO production, and this mechanism may be in part mediated by a neural reflex through vagal efferent nerves, resulting from the pressor response to L-NAME.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Ohuchi
T
T
Tachibana
M
M
Okabe
S
S
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000098:blood supply / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy; D015016:Yohimbine / Q000494:pharmacology
D001639:Bicarbonates; D015016:Yohimbine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin