Role of endogenous nitric oxide in the control of gastric acid secretion, blood flow and gastrin release in conscious dogs.
Nitric oxide (NO) was shown to mediate gastric hyperemia following secretory stimulation but its role in the control of gastric secretion has not been clarified. Secretory studies were carried out on conscious dogs with chronic gastric fistula, Heidenhain pouch and esophageal fistula, while changes in gastric blood flow were measured in the mucosa of Heidenhain pouuch by laser Doppler flowmetry. Plasma gastrin was determined by radioimmunoassay. Infusion of NG-nitro-L-arginine (L-NNA) (bolus i.v. injection of 2.5 mg/kg followed by infusion of 0.5 mg/kg/h), a potent inhibitor of nitric oxide synthase, failed to affect basal gastric secretion or plasma gastrin level but suppressed an increase of this secretion induced by sham-feeding, ordinary meat feeding or i.v. infusion of bombesin (0.5 microgram/kg/h), pentagastrin (4 micrograms/kg/h) or histamine (40 micrograms/kg/h). In tests with feeding and bombesin infusion, L-NNA caused a significant and dose-dependent reduction in plasma gastrin levels. The inhibition by L-NNA of gastric acid secretory response to pentagastrin, histamine or feeding was accompanied by a decline in blood flow. Addition of L-arginine (bolus i.v. dose of 50 mg/kg followed by infusion of 5 mg/kg/h) significantly attenuated the L-NNA induced inhibition of gastric secretion and the reduction in plasma gastrin response as well as in the fall of gastric blood flow. We conclude that endogenous nitric oxide affects the gastric secretion and that this effect is mediated, at least in part, by the changes in the gastrin release and gastric blood flow.
Bilski
J
J
Institute of Physiology, University School of Medicine, Krakow, Poland.
Konturek
P C
PC
Konturek
S J
SJ
Cieszkowski
M
M
Czarnobilski
K
K
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001839:Bombesin / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D004435:Eating; D005402:Fistula; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D005755:Gastrins / Q000378:metabolism*; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D009130:Muscle, Smooth / Q000098:blood supply; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D010418:Pentagastrin / Q000008:administration & dosage / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013270:Stomach / Q000098:blood supply*; D013997:Time Factors
D005755:Gastrins; D019335:Nitroarginine; D009569:Nitric Oxide; D006632:Histamine; D001120:Arginine; D010418:Pentagastrin; D001839:Bombesin