Vagally stimulated gastric acid and pancreatic enzyme secretion-different roles of nitric oxide (NO)

Abstract

In 6 conscious dogs with chronic gastric and duodenal fistulas we compared the effect of the cholinerigic MI-receptor antagonist telenzepine (81 nmol/kg/h iv.) and the nitric oxide synthase inhibitor N°-nitro-L-arginine (L-NNA; 2.5 mg/kg + 0.5 mg/kg/h iv.) on the pancreatic protein response to graded loads of intraduodenal tryptophan (0.37-10.0 mmol/h), given against a background of secretin (20.5 pmol/kg/h iv.). The incremental protein output (i.e. observed protein output minus the response to secretin alone) was calculated. Results: Telenezpine and L-NNA significantly (p<0.05) decreased the pancreatic protein output during secretin infusion by 84 % and 68 %, respectively. Tryptophan dose-dependently increased the protein output over that seen with secretin alone. Both telenzepine and L-NNA significantly decreased the incremental protein responses to the lower loads (0.37-3.3 mmol/h) of tryptophan by 77 to 87 % and by 70 to 84 %, respectively. Neither telenzepine nor L-NNA had a significant effect on the incremental protein response to the highest load (10.0 mmolJh) of tryptophan. Conclusions: In dogs, 1) Ml-receptors and endogenous nitric oxide are stimulatory mediators of the basal pancreatic protein output and the protein response to lower loads of intraduodenal tryptophan; 2) the similar inhibitory pattern of the antagonists of these mediators indicate that both Ml-receptors and nitric oxide take part in the same pathway to stimulate pancreatic enzyme output; 3) the pancreatic enzyme response to high loads of tryptophan is mainly controlled by other (probably humoral) mediators.