Role of endogenous nitric oxide in the control of exocrine and endocrine pancreatic secretion in humans.
BACKGROUND
Nitric oxide (NO) is an unstable vasodilator formed by NO synthetase (NOS) from L-arginine (L-Arg) in various cells but its role in the control of pancreatic secretion in humans has not been examined.


OBJECTIVE
This study was designed to determine the role of endogenous NO in the control of exocrine and endocrine pancreas using NOS inhibitor, NG-monomethyl-L-Arg (L-NMMA).


METHODS
Pancreatic secretion was stimulated by intravenous infusion of secretin (80 pmol/kg/h) plus caerulein (50 pmol/kg/h) and duodenal content was aspirated by gastroduodenal tube. Two series of tests with secretagogue infusion were performed, one, with addition of graded doses of L-NMMA and, another, with addition of a constant dose of L-Arg alone followed by L-NMMA alone and finally by a combination of L-Arg and L-NMMA.


RESULTS
Addition of L-NMMA in graded doses (2-8 mumol/kg/h) reduced dose dependently the secretin-caerulein stimulated pancreatic enzyme secretion without alterations in the volume flow and bicarbonate outputs. The addition of L-Arg to L-NMMA reversed the inhibitory action of L-NMMA on protein enzyme response to secretin-caerulein in these subjects. Secretin-caerulein infusion caused significant increase in plasma insulin and pancreatic polypeptide levels but without changes in plasma glucagon or somatostatin levels. L-NMMA alone resulted in a significant fall in plasma insulin and pancreatic polypeptide levels, while L-Arg added to pancreatic secretagogue infusion caused a significant increase of plasma insulin and pancreatic polypeptide levels above those attained with secretagogues alone. After the addition of L-Arg to L-NMMA, both plasma insulin and pancreatic polypeptide levels rose significantly above the levels observed with L-NMMA plus secretin-CCK stimulation.


CONCLUSIONS
This study provides evidence that the suppression of NOS reduces pancreatic enzyme secretion and the plasma insulin and pancreatic polypeptide levels suggesting that endogenous NO affects both exocrine and endocrine pancreatic secretion in humans.
Konturek
J W
JW
Department of Medicine B, University of Münster, Germany.
Hengst
K
K
Kulesza
E
E
Gabryelewicz
A
A
Konturek
S J
SJ
Domschke
W
W
D000328:Adult; D000681:Amylases / Q000187:drug effects / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology*; D002108:Ceruletide / Q000494:pharmacology; D002918:Chymotrypsin / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology; D008049:Lipase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010187:Pancreatic Hormones / Q000378:metabolism*; D010189:Pancreatic Juice / Q000187:drug effects; D012633:Secretin / Q000494:pharmacology; D014357:Trypsin / Q000187:drug effects / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
D005765:Gastrointestinal Agents; D010187:Pancreatic Hormones; D012633:Secretin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D002108:Ceruletide; D001120:Arginine; D019001:Nitric Oxide Synthase; D008049:Lipase; D000681:Amylases; D002918:Chymotrypsin; D014357:Trypsin