Differential roles of endogenous nitric oxide on neural regulation of basal exocrine pancreatic secretion in intact and denervated pancreas

Background. Autonomic nerves and humoral factors regulate pancreatic secretion. Nerves containing nitric oxide (NO) synthase (NOS) are in close proximity and located within cholinergic, adrenergic and sensory nerve bundles. Yet, the interactive mechanisms between various nerve populations remain elusive. Aims: To evaluate the role of endogenous NO in basal exocrine pancreatic secretion in the extrinsically denervated rat pancreas. Methods: Male Sprague-Dawley rats were assigned to 2 groups of 11 animals. The first group of sham-operated animals served as controls. In the second group extrinsic pancreatic innervation was surgically interrupted. One week later, after selective catheterization of the celiac axis and the bile-pancreatic duct, the animals received intra-arterial infusions of N-G-nitro-L-arginine (L-NNA; 0.48 mg/kg b.w./h) followed by intraarterial infusions of L-arginine (110 mg/kg b.w./h). Total protein and amylase were measured in bile-pancreatic secretions collected at 15-min intervals. Results: In controls, total protein and amylase output showed a biphasic secretion pattern with an increase during L-NNA infusion followed by a decrease when the infusion ceased and further augmentation 1 h later. In denervated animals, L-NNA caused a sustained decrease in pancreatic secretion followed by an increase 1 h later. Infusion of L-arginine at the time of maximum decrease slowed the second phase of protein and amylase output in sham-operated rats, but accentuated the onset of secretion in denervated animals. Conclusion: Inhibition of endogenous NO release was shown to increase baseline secretion in the intact pancreas. Superposition of extrinsic denervation on neural NOS-blockade decreased basal exocrine secretion, indicating that intra-pancreatic NO release is regulated by extra-pancreatic nerves. Copyright (C) 2001 S. Karger AG, Basel and IAP.