The role of nitric oxide in edema formation in L-arginine-induced acute pancreatitis

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Abstract

Introduction: Nitric oxide (NO) has been implicated in the regulation of the pancreatic circulation, the promotion of the capillary integrity, and the inhibition of leukocyte adhesion. Aims: To investigate the rates of changes in the pancreatic constitutive NO synthase (cNOS) and inducible NOS (iNOS) activities and the role of NO in the vascular permeability changes during the development of L-arginine (Arg)-induced acute pancreatitis. Methodology: Acute pancreatitis was induced in male Wistar rats by injecting 250 mg/100 g body weight of Arg i.p. twice at an interval of 1 hour, as a 20% solution in 0.15 M NACl (group I). The control rats received the same quantity of glycine (group II). In group III, 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME) was injected i.p. 19 hours after the first Arg injection. The rats were killed at 6, 12, 24, or 48 hours following Arg administration, and the plasma amylase concentration and the pancreatic weight/body weight (pw/bw) ratios were evaluated. NOS activity was determined via the conversion of L-14C-Arg monohydrochloride to 14Ccitrulline. The vascular permeability was examined by means of the extravasation of Evans blue dye (20 mg/kg bw) into the pancreatic tissue. Results: The serum amylase level was already increased at 6 hours in group I animals, peaked at 12 hours after the Arg injection (11.800 ± 590 versus 6.618 ± 252 U/L in group II), and returned to the control level at 48 hours. The pw/bw ratio peaked at 24 hours in group I (6.63 ± 0.52 versus 4.02 ± 0.22 mg/g in group II) and returned to the control level at 48 hours. The cNOS activity was depleted at 6 hours in group I (0.02 ± 0.003 versus 0.23 ± 0.02 pmol/min/mg protein in group II); it then gradually increased to a level significantly higher than that in group II and decreased thereafter (0.45 ± 0.03 and 0.13 ± 0.01 pmol/min/mg protein at 24 and 48 hours). The iNOS activity was significantly increased at 24 and 48 hours versus that in group II (0.15 ± 0.05 and 0.07 ± 0.01 versus 0.04 ± 0.01 pmol/min/mg protein). The pancreatic concentration of Evans blue dye was significantly higher in group I than in group II (138.59 ± 11.04 versus 43.57 ± 2.67 (g/dry weight). Treatment with L-NAME significantly reduced the amylase activity, pw/bw, Evans blue concentration, and cNOS activity of the pancreas but did not exert any beneficial effect on the histologic score at 24 hours after the onset of pancreatitis, as compared with those values in group I (6.528 ± 673 U/L, 4.56 ± 0.65 mg/g, 86.84 ± 3.9 (g/dry weight, 0.14 ± 0.04 pmol/min/mg protein). Conclusion: Endogenous NO is involved in the formation of pancreatic edema in Arg-induced acute pancreatitis by increasing the vascular permeability and protein extravasation. L-NAME treatment decreased the cNOS activity and edema formation but did not prevent the histologic damage in Arg-induced acute pancreatitis.

Original languageEnglish
Pages (from-to)277-282
Number of pages6
JournalPancreas.
Volume25
Issue number3
DOIs
Publication statusPublished - okt. 2002

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Pancreatitis
Arginine
Edema
Nitric Oxide
NG-Nitroarginine Methyl Ester
Evans Blue
Capillary Permeability
Weights and Measures
Amylases
Body Weight
Nitric Oxide Synthase
Proteins
Coloring Agents
Injections
Nitric Oxide Synthase Type II
Glycine
Wistar Rats
Pancreas
Leukocytes
Serum

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

Cite this

@article{98113d03302c489f80edb99f7314f73b,
title = "The role of nitric oxide in edema formation in L-arginine-induced acute pancreatitis",
abstract = "Introduction: Nitric oxide (NO) has been implicated in the regulation of the pancreatic circulation, the promotion of the capillary integrity, and the inhibition of leukocyte adhesion. Aims: To investigate the rates of changes in the pancreatic constitutive NO synthase (cNOS) and inducible NOS (iNOS) activities and the role of NO in the vascular permeability changes during the development of L-arginine (Arg)-induced acute pancreatitis. Methodology: Acute pancreatitis was induced in male Wistar rats by injecting 250 mg/100 g body weight of Arg i.p. twice at an interval of 1 hour, as a 20{\%} solution in 0.15 M NACl (group I). The control rats received the same quantity of glycine (group II). In group III, 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME) was injected i.p. 19 hours after the first Arg injection. The rats were killed at 6, 12, 24, or 48 hours following Arg administration, and the plasma amylase concentration and the pancreatic weight/body weight (pw/bw) ratios were evaluated. NOS activity was determined via the conversion of L-14C-Arg monohydrochloride to 14Ccitrulline. The vascular permeability was examined by means of the extravasation of Evans blue dye (20 mg/kg bw) into the pancreatic tissue. Results: The serum amylase level was already increased at 6 hours in group I animals, peaked at 12 hours after the Arg injection (11.800 ± 590 versus 6.618 ± 252 U/L in group II), and returned to the control level at 48 hours. The pw/bw ratio peaked at 24 hours in group I (6.63 ± 0.52 versus 4.02 ± 0.22 mg/g in group II) and returned to the control level at 48 hours. The cNOS activity was depleted at 6 hours in group I (0.02 ± 0.003 versus 0.23 ± 0.02 pmol/min/mg protein in group II); it then gradually increased to a level significantly higher than that in group II and decreased thereafter (0.45 ± 0.03 and 0.13 ± 0.01 pmol/min/mg protein at 24 and 48 hours). The iNOS activity was significantly increased at 24 and 48 hours versus that in group II (0.15 ± 0.05 and 0.07 ± 0.01 versus 0.04 ± 0.01 pmol/min/mg protein). The pancreatic concentration of Evans blue dye was significantly higher in group I than in group II (138.59 ± 11.04 versus 43.57 ± 2.67 (g/dry weight). Treatment with L-NAME significantly reduced the amylase activity, pw/bw, Evans blue concentration, and cNOS activity of the pancreas but did not exert any beneficial effect on the histologic score at 24 hours after the onset of pancreatitis, as compared with those values in group I (6.528 ± 673 U/L, 4.56 ± 0.65 mg/g, 86.84 ± 3.9 (g/dry weight, 0.14 ± 0.04 pmol/min/mg protein). Conclusion: Endogenous NO is involved in the formation of pancreatic edema in Arg-induced acute pancreatitis by increasing the vascular permeability and protein extravasation. L-NAME treatment decreased the cNOS activity and edema formation but did not prevent the histologic damage in Arg-induced acute pancreatitis.",
keywords = "Arg-induced pancreatitis, Constitutive NO synthase, Inducible NO synthase, Pancreatic edema, Vascular permeability",
author = "T. Tak{\'a}cs and L. Czak{\'o} and E. Morschl and F. L{\'a}szl{\'o} and L. Tiszlavicz and Z. Rakonczay and J. Lonovics",
year = "2002",
month = "10",
doi = "10.1097/00006676-200210000-00010",
language = "English",
volume = "25",
pages = "277--282",
journal = "Pancreas",
issn = "0885-3177",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - The role of nitric oxide in edema formation in L-arginine-induced acute pancreatitis

AU - Takács, T.

AU - Czakó, L.

AU - Morschl, E.

AU - László, F.

AU - Tiszlavicz, L.

AU - Rakonczay, Z.

AU - Lonovics, J.

PY - 2002/10

Y1 - 2002/10

N2 - Introduction: Nitric oxide (NO) has been implicated in the regulation of the pancreatic circulation, the promotion of the capillary integrity, and the inhibition of leukocyte adhesion. Aims: To investigate the rates of changes in the pancreatic constitutive NO synthase (cNOS) and inducible NOS (iNOS) activities and the role of NO in the vascular permeability changes during the development of L-arginine (Arg)-induced acute pancreatitis. Methodology: Acute pancreatitis was induced in male Wistar rats by injecting 250 mg/100 g body weight of Arg i.p. twice at an interval of 1 hour, as a 20% solution in 0.15 M NACl (group I). The control rats received the same quantity of glycine (group II). In group III, 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME) was injected i.p. 19 hours after the first Arg injection. The rats were killed at 6, 12, 24, or 48 hours following Arg administration, and the plasma amylase concentration and the pancreatic weight/body weight (pw/bw) ratios were evaluated. NOS activity was determined via the conversion of L-14C-Arg monohydrochloride to 14Ccitrulline. The vascular permeability was examined by means of the extravasation of Evans blue dye (20 mg/kg bw) into the pancreatic tissue. Results: The serum amylase level was already increased at 6 hours in group I animals, peaked at 12 hours after the Arg injection (11.800 ± 590 versus 6.618 ± 252 U/L in group II), and returned to the control level at 48 hours. The pw/bw ratio peaked at 24 hours in group I (6.63 ± 0.52 versus 4.02 ± 0.22 mg/g in group II) and returned to the control level at 48 hours. The cNOS activity was depleted at 6 hours in group I (0.02 ± 0.003 versus 0.23 ± 0.02 pmol/min/mg protein in group II); it then gradually increased to a level significantly higher than that in group II and decreased thereafter (0.45 ± 0.03 and 0.13 ± 0.01 pmol/min/mg protein at 24 and 48 hours). The iNOS activity was significantly increased at 24 and 48 hours versus that in group II (0.15 ± 0.05 and 0.07 ± 0.01 versus 0.04 ± 0.01 pmol/min/mg protein). The pancreatic concentration of Evans blue dye was significantly higher in group I than in group II (138.59 ± 11.04 versus 43.57 ± 2.67 (g/dry weight). Treatment with L-NAME significantly reduced the amylase activity, pw/bw, Evans blue concentration, and cNOS activity of the pancreas but did not exert any beneficial effect on the histologic score at 24 hours after the onset of pancreatitis, as compared with those values in group I (6.528 ± 673 U/L, 4.56 ± 0.65 mg/g, 86.84 ± 3.9 (g/dry weight, 0.14 ± 0.04 pmol/min/mg protein). Conclusion: Endogenous NO is involved in the formation of pancreatic edema in Arg-induced acute pancreatitis by increasing the vascular permeability and protein extravasation. L-NAME treatment decreased the cNOS activity and edema formation but did not prevent the histologic damage in Arg-induced acute pancreatitis.

AB - Introduction: Nitric oxide (NO) has been implicated in the regulation of the pancreatic circulation, the promotion of the capillary integrity, and the inhibition of leukocyte adhesion. Aims: To investigate the rates of changes in the pancreatic constitutive NO synthase (cNOS) and inducible NOS (iNOS) activities and the role of NO in the vascular permeability changes during the development of L-arginine (Arg)-induced acute pancreatitis. Methodology: Acute pancreatitis was induced in male Wistar rats by injecting 250 mg/100 g body weight of Arg i.p. twice at an interval of 1 hour, as a 20% solution in 0.15 M NACl (group I). The control rats received the same quantity of glycine (group II). In group III, 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME) was injected i.p. 19 hours after the first Arg injection. The rats were killed at 6, 12, 24, or 48 hours following Arg administration, and the plasma amylase concentration and the pancreatic weight/body weight (pw/bw) ratios were evaluated. NOS activity was determined via the conversion of L-14C-Arg monohydrochloride to 14Ccitrulline. The vascular permeability was examined by means of the extravasation of Evans blue dye (20 mg/kg bw) into the pancreatic tissue. Results: The serum amylase level was already increased at 6 hours in group I animals, peaked at 12 hours after the Arg injection (11.800 ± 590 versus 6.618 ± 252 U/L in group II), and returned to the control level at 48 hours. The pw/bw ratio peaked at 24 hours in group I (6.63 ± 0.52 versus 4.02 ± 0.22 mg/g in group II) and returned to the control level at 48 hours. The cNOS activity was depleted at 6 hours in group I (0.02 ± 0.003 versus 0.23 ± 0.02 pmol/min/mg protein in group II); it then gradually increased to a level significantly higher than that in group II and decreased thereafter (0.45 ± 0.03 and 0.13 ± 0.01 pmol/min/mg protein at 24 and 48 hours). The iNOS activity was significantly increased at 24 and 48 hours versus that in group II (0.15 ± 0.05 and 0.07 ± 0.01 versus 0.04 ± 0.01 pmol/min/mg protein). The pancreatic concentration of Evans blue dye was significantly higher in group I than in group II (138.59 ± 11.04 versus 43.57 ± 2.67 (g/dry weight). Treatment with L-NAME significantly reduced the amylase activity, pw/bw, Evans blue concentration, and cNOS activity of the pancreas but did not exert any beneficial effect on the histologic score at 24 hours after the onset of pancreatitis, as compared with those values in group I (6.528 ± 673 U/L, 4.56 ± 0.65 mg/g, 86.84 ± 3.9 (g/dry weight, 0.14 ± 0.04 pmol/min/mg protein). Conclusion: Endogenous NO is involved in the formation of pancreatic edema in Arg-induced acute pancreatitis by increasing the vascular permeability and protein extravasation. L-NAME treatment decreased the cNOS activity and edema formation but did not prevent the histologic damage in Arg-induced acute pancreatitis.

KW - Arg-induced pancreatitis

KW - Constitutive NO synthase

KW - Inducible NO synthase

KW - Pancreatic edema

KW - Vascular permeability

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U2 - 10.1097/00006676-200210000-00010

DO - 10.1097/00006676-200210000-00010

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C2 - 12370539

AN - SCOPUS:0036786168

VL - 25

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EP - 282

JO - Pancreas

JF - Pancreas

SN - 0885-3177

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