Interactions of pro-inflammatory and vasoactive mediators with nitric oxide in the regulation of rat vascular permeability during laparotomy

Imre Pávó, József Pozsár, Éva Morschl, János Nemcsik, Ferenc László, Brendan J.R. Whittle

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2 Citations (Scopus)

Abstract

Inhibition of constitutive nitric oxide (NO) synthases by administration of N(G)-nitro-L-arginine methyl ester (L-NAME) during abdominal laparotomy provokes extensive vascular leakage in the rat gastrointestinal tract, assessed by the extravasation of [125I]human serum albumin. In the present study, the role of vasoactive or neutrophil-derived pro-inflammatory mediators in this process has been investigated. Administration of the thromboxane synthase inhibitor, 1-benzyl-imidazole (BZI, 25-50 mg kg-1, s.c.), the platelet-activating factor (PAF) receptor antagonist, 3-[4-(2- chlorophenyl)-9-methyl-6H-thienol-[3,2-f][1,2,4]-triazolo-[4,3-a][1,4]- diazepine-2-yl]-1-(4-morpholynil)-1-propionate (WEB 2086; 0.5-1 mg kg-1, s.c.), the 5-lipoxygenase synthase inhibitor, N-(4-benzyloxybenzyl)- acetohydroxamic acid (BW A137C; 4-20 mg kg-1, s.c.) or the vasopressin pressor receptor antagonist ([Mca1,Tyr(Me)2,Arg8]vasopressin/Manning peptide; 0.01-0.2 μg kg-1, s.c.) dose-dependently reduced the intestinal plasma leakage provoked by L-NAME (5 mg kg-1, s.c.), following a 5-cm abdominal laparotomy in anaesthetised rats. These findings suggest that constitutive NO synthase effectively counteracts the damaging actions on microvascular integrity of mediators, including thromboxanes, PAF, leukotrienes and vasopressin, released during surgical intervention. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)193-197
Number of pages5
JournalEuropean Journal of Pharmacology
Volume402
Issue number1-2
DOIs
Publication statusPublished - Aug 18 2000

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Keywords

  • Leukotrienes
  • Neutrophil granulocytes
  • Nitric oxide (NO)
  • Platelet-activating factor (PAF)
  • Surgery
  • Thromboxanes
  • Vascular endothelium
  • Vascular permeability
  • Vasopressin

ASJC Scopus subject areas

  • Pharmacology

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