The involvement of endogenous nitric oxide in vagal-cholinergic stimulation of exocrine and endocrine pancreas in dogs.
Previous studies showed that nitric oxide (NO), synthesized from L-arginine (L-arg) by NO synthase (NOS) in vascular epithelium and nerve terminals, affects exocrine pancreatic secretion, but its role in control of endocrine pancreas has not been studied. In this study, the role of NO in the control of pancreatic secretion in response to vagal-cholinergic stimulation and duodenal infusion of nutrients was determined in conscious dogs with chronic pancreatic fistulas. Sham feeding (SF), urecholine iv infusion, and duodenal perfusion with nutrients were used to stimulate the pancreatic protein secretion, and insulin and glucagon release in tests without and with iv infusion of NG-nitro-L-arginine (L-NNA), an inhibitor of NO synthase, L-arg, a substrate of NOS, or their combination was used. SF, urecholine, and duodenal nutrient resulted in the stimulation of pancreatic protein secretion reaching, respectively, 50, 20, and 42% of cerulein maximum. Infusion of L-arg almost doubled the basal protein secretion and tended to increase the secretory response to SF and duodenal nutrient. After infusion of L-NNA, the pancreatic secretory responses to SF, urecholine, and duodenal nutrient were inhibited by about 70, 30, and 75%, respectively. When L-arg was combined with L-NNA, the reduction in pancreatic secretion by L-NNA was significantly attenuated. SF resulted in a significant rise in plasma insulin and glucagon, and this response was completely abolished by L-NNA infusion. Urecholine and duodenal nutrient also resulted in a marked increment in plasma insulin and glucagon, the insulin (but not glucagon) increment being abolished by the pretreatment with L-NNA and reversed by the addition of L-arg.(ABSTRACT TRUNCATED AT 250 WORDS)
Bilski
J
J
Institute of Physiology, University School of Medicine, Krakow, Poland.
Konturek
J W
JW
Konturek
S J
SJ
Domschke
W
W
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001626:Bethanechol Compounds / Q000494:pharmacology; D004285:Dogs; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000294:innervation / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D010179:Pancreas / Q000294:innervation / Q000378:metabolism*; D014630:Vagus Nerve / Q000502:physiology*
D001626:Bethanechol Compounds; D007328:Insulin; D019335:Nitroarginine; D009569:Nitric Oxide; D005934:Glucagon; D001120:Arginine