Endogenous nitric oxide in the maintenance of rat microvascular integrity against widespread plasma leakage following abdominal laparotomy

F. László, Brendan J R Whittle

Research output: Article

5 Citations (Scopus)

Abstract

1. The role of nitric oxide (NO) in the maintenance of microvascular integrity during minor surgical manipulation has been evaluated in the rat. 2. The NO synthase inhibitors, N(G)-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1, s.c.) and N(G)-monomethyl-L-arginine (L-NMMA, 50 mg kg-1, s.c.) had no effect on microvascular leakage of radiolabelled albumin over 1 h in the stomach, duodenum, jejunum, colon, lung and kidney in the un-operated conscious or pentobarbitone-anaesthetized rat. 3. In contrast, in anaesthetized rats with a midline abdominal laparotomy (5 cm), L-NAME (1-5 mg kg-1, s.c.) or L-NMMA (12.5-50 mg kg-1, s.c.) dose-dependently increased gastrointestinal, renal and pulmonary vascular leakage, effects reversed by L-arginine pretreatment (300 mg kg-1, s.c., 15 min). These actions were not observed in anaesthetized rats that had only received a midline abdominal skin incision (5 cm). 4. Pretreatment with a rabbit anti-rat neutrophil serum (0.4 ml kg-1, i.p.), 4 h before laparotomy, abolished the plasma leakage induced by L-NAME in all the organs investigated. 5. These results indicate that the following abdominal laparotomy, inhibition of constitutive NO synthase provokes vascular leakage in the general microcirculation, by a process that may involve neutrophils. Such effects could thus confound studies on the microvascular actions of NO synthase inhibitors using acute surgically prepared in vivo models. The findings thus suggest that constitutively-formed NO has a crucial role in the maintenance of acute microvascular integrity following abdominal surgical intervention.

Original languageEnglish
Pages (from-to)515-521
Number of pages7
JournalBritish Journal of Pharmacology
Volume126
Issue number2
DOIs
Publication statusPublished - 1999

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Laparotomy
NG-Nitroarginine Methyl Ester
Nitric Oxide
Maintenance
Nitric Oxide Synthase
omega-N-Methylarginine
Blood Vessels
Arginine
Neutrophils
Kidney
Lung
Pentobarbital
Jejunum
Microcirculation
Duodenum
Albumins
Stomach
Colon
Rabbits
Skin

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Endogenous nitric oxide in the maintenance of rat microvascular integrity against widespread plasma leakage following abdominal laparotomy",
abstract = "1. The role of nitric oxide (NO) in the maintenance of microvascular integrity during minor surgical manipulation has been evaluated in the rat. 2. The NO synthase inhibitors, N(G)-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1, s.c.) and N(G)-monomethyl-L-arginine (L-NMMA, 50 mg kg-1, s.c.) had no effect on microvascular leakage of radiolabelled albumin over 1 h in the stomach, duodenum, jejunum, colon, lung and kidney in the un-operated conscious or pentobarbitone-anaesthetized rat. 3. In contrast, in anaesthetized rats with a midline abdominal laparotomy (5 cm), L-NAME (1-5 mg kg-1, s.c.) or L-NMMA (12.5-50 mg kg-1, s.c.) dose-dependently increased gastrointestinal, renal and pulmonary vascular leakage, effects reversed by L-arginine pretreatment (300 mg kg-1, s.c., 15 min). These actions were not observed in anaesthetized rats that had only received a midline abdominal skin incision (5 cm). 4. Pretreatment with a rabbit anti-rat neutrophil serum (0.4 ml kg-1, i.p.), 4 h before laparotomy, abolished the plasma leakage induced by L-NAME in all the organs investigated. 5. These results indicate that the following abdominal laparotomy, inhibition of constitutive NO synthase provokes vascular leakage in the general microcirculation, by a process that may involve neutrophils. Such effects could thus confound studies on the microvascular actions of NO synthase inhibitors using acute surgically prepared in vivo models. The findings thus suggest that constitutively-formed NO has a crucial role in the maintenance of acute microvascular integrity following abdominal surgical intervention.",
keywords = "Constitutive nitric oxide synthase, eNOS, Laparotomy, Neutrophils, Nitric oxide synthase inhibitors, Plasma loss, Surgery, Vascular permeability",
author = "F. L{\'a}szl{\'o} and Whittle, {Brendan J R}",
year = "1999",
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T1 - Endogenous nitric oxide in the maintenance of rat microvascular integrity against widespread plasma leakage following abdominal laparotomy

AU - László, F.

AU - Whittle, Brendan J R

PY - 1999

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N2 - 1. The role of nitric oxide (NO) in the maintenance of microvascular integrity during minor surgical manipulation has been evaluated in the rat. 2. The NO synthase inhibitors, N(G)-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1, s.c.) and N(G)-monomethyl-L-arginine (L-NMMA, 50 mg kg-1, s.c.) had no effect on microvascular leakage of radiolabelled albumin over 1 h in the stomach, duodenum, jejunum, colon, lung and kidney in the un-operated conscious or pentobarbitone-anaesthetized rat. 3. In contrast, in anaesthetized rats with a midline abdominal laparotomy (5 cm), L-NAME (1-5 mg kg-1, s.c.) or L-NMMA (12.5-50 mg kg-1, s.c.) dose-dependently increased gastrointestinal, renal and pulmonary vascular leakage, effects reversed by L-arginine pretreatment (300 mg kg-1, s.c., 15 min). These actions were not observed in anaesthetized rats that had only received a midline abdominal skin incision (5 cm). 4. Pretreatment with a rabbit anti-rat neutrophil serum (0.4 ml kg-1, i.p.), 4 h before laparotomy, abolished the plasma leakage induced by L-NAME in all the organs investigated. 5. These results indicate that the following abdominal laparotomy, inhibition of constitutive NO synthase provokes vascular leakage in the general microcirculation, by a process that may involve neutrophils. Such effects could thus confound studies on the microvascular actions of NO synthase inhibitors using acute surgically prepared in vivo models. The findings thus suggest that constitutively-formed NO has a crucial role in the maintenance of acute microvascular integrity following abdominal surgical intervention.

AB - 1. The role of nitric oxide (NO) in the maintenance of microvascular integrity during minor surgical manipulation has been evaluated in the rat. 2. The NO synthase inhibitors, N(G)-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1, s.c.) and N(G)-monomethyl-L-arginine (L-NMMA, 50 mg kg-1, s.c.) had no effect on microvascular leakage of radiolabelled albumin over 1 h in the stomach, duodenum, jejunum, colon, lung and kidney in the un-operated conscious or pentobarbitone-anaesthetized rat. 3. In contrast, in anaesthetized rats with a midline abdominal laparotomy (5 cm), L-NAME (1-5 mg kg-1, s.c.) or L-NMMA (12.5-50 mg kg-1, s.c.) dose-dependently increased gastrointestinal, renal and pulmonary vascular leakage, effects reversed by L-arginine pretreatment (300 mg kg-1, s.c., 15 min). These actions were not observed in anaesthetized rats that had only received a midline abdominal skin incision (5 cm). 4. Pretreatment with a rabbit anti-rat neutrophil serum (0.4 ml kg-1, i.p.), 4 h before laparotomy, abolished the plasma leakage induced by L-NAME in all the organs investigated. 5. These results indicate that the following abdominal laparotomy, inhibition of constitutive NO synthase provokes vascular leakage in the general microcirculation, by a process that may involve neutrophils. Such effects could thus confound studies on the microvascular actions of NO synthase inhibitors using acute surgically prepared in vivo models. The findings thus suggest that constitutively-formed NO has a crucial role in the maintenance of acute microvascular integrity following abdominal surgical intervention.

KW - Constitutive nitric oxide synthase

KW - eNOS

KW - Laparotomy

KW - Neutrophils

KW - Nitric oxide synthase inhibitors

KW - Plasma loss

KW - Surgery

KW - Vascular permeability

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