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Background: Endogenous nitric oxide has been implicated in the control of mesenteric circulation, but its role in the control of pancreatic blood flow and exocrine pancreatic secretion has not been studied., Methods: Secretory studies were performed on conscious dogs with chronic pancreatic fistulas, and changes in pancreatic blood flow were measured by laser Doppler flowmetry in anesthetized animals., Results: Infusion of NG-nitro-L-arginine did not affect basal pancreatic protein secretion but suppressed an increase of this secretion induced by L-arginine but not that induced by glyceryl trinitrate. Sham-feeding, meal feeding, and infusion of secretin plus cholecystokinin induced pancreatic protein outputs reaching, respectively, 30%, 74%, and 50% of cerulein maximum in these dogs. Infusion of NG-nitro-L-arginine caused a profound inhibition of these secretions, whereas the addition of L-arginine reversed this inhibition in part. NG-nitro-L-arginine or L-arginine added to the incubation medium of isolated canine pancreatic acini did not affect basal or cholecystokinin-induced amylase release. In anesthetized dogs, infusion of NG-nitro-L-arginine caused a significant reduction in the pancreatic blood flow both while resting and following stimulation with secretin plus cholecystokinin but did not affect this flow in animals treated with glyceryl trinitrate. Addition of L-arginine attenuated the decrease in pancreatic blood flow and the increase in systemic blood pressure caused by NG-L-nitro-arginine., Conclusions: Endogenous NO affects pancreatic secretion probably through the changes in the vascular bed.

An in vivo canine gastric chamber preparation was used to determine effects of exogenous cyclic AMP and dibutyryl cyclic AMP on histamine-driven acid secretion and the role of blood flow in these responses. Histamine was infused intravenously at a submaximal rate 1.2 mu/kg-min) followed by the intraarterial infusion of either cyclic AMP (0.15 mg/kg-min) or dibutyryl cyclic AMP (0.15 mg/kg-min. Acid secretion and mucosal blood flow (aminopyrine clearance) were measured at 15-minute intervals, and electrical potential difference was measured continuously. Histamine alone decreased the potential difference from 82 mV to 48 mV within 60 minutes, increased aminopyrine clearance from 1.0 ml/min to 2.4 ml/min and increased acid output to 220 muEq/15 min. All values returned towards control following termination of histamine infusion. Dibutyryl cyclic AMP significantly increased histamine stimulated acid secretion to 350 muEq/15 min, but did not alter mucosal blood flow or electrical potential. Cyclic AMP did not change secretory, circulatory or electrical response to histamine. Therefore, dibutyryl cyclic AMP appears to increase histamine-stimulated acid secretion, and the effect is not mediated by increased mucosal blood flow.

The electrophysiological effects of two potent inhibitors of gastric acid secretion, burimamide and 16,16-dimethyl prostaglandin E2 (dm-PGE2), were determined in an in vivo histamine-stimulated canine stomach preparation and an in vitro canine gastric mucosal preparation. In the in vivo stomach preparation, intravenous burimamide caused a decrease in acid secretion, an increase in transmucosal potential difference (PD) and the relative resistance (R) was essentially unchanged. Intravenous dm-PGE2 also inhibited acid secretion and increased PD but, in contrast to burimamide, increased R. In the in vitro preparation, the unidirectional flux of sodium from mucosa to serosa increased after dm-PGE2 but not after burimamide. Passive sodium fluxes and unidirectional chloride fluxes were not altered after either agent. These findings suggest that increased active transport of sodium from mucosa to serosa is at least partially responsible for the observed increase in transmural PD with dm-PGE2, an agent which also decreases hydrogen ion transport. With burimamide the increased PD was due primarily to inhibition of hydrogen ion secretion.

Peptide YY (PYY) is released by perfusion of an ileocolonic segment with oleate and inhibits exocrine pancreatic secretion. This study was designed to determine the role of the adrenergic pathway in the PYY-induced inhibition of pancreatic secretion. After intravenous administration of PYY, there was a dose-dependent inhibition of pancreatic HCO3 and protein responses to secretin, cholecystokinin, and feeding in conscious dogs and a reduction in pancreatic blood flow in anesthetized animals. These inhibitory effects of PYY on pancreatic secretion and blood flow were abolished in the presence of combined phentolamine and propranolol. Ileal perfusion with oleate caused a rise in plasma PYY levels similar to that observed after intravenous infusion of exogenous PYY. Combined alpha- and beta-adrenergic blockade also antagonized the effects of ileal perfusion with oleate on hormonal and postprandial pancreatic secretion. We conclude that exogenous PYY or endogenous PYY released by ileal oleate inhibits pancreatic secretory responses to exogenous secretin, cholecystokinin, or a meal and causes pancreatic vasoconstriction. Both these effects are mediated, at least in part, by the adrenergic pathway.