Actions of isoform-selective and non-selective nitric oxide synthase inhibitors on endotoxin-induced vascular leakage in rat colon

F. László, Brendan J R Whittle

Research output: Contribution to journalArticle

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Abstract

The effects of the nitric oxide (NO) synthase inhibitor, N-(3-(aminomethyl)benzyl)-acetamidine (1400W) which is selective for the inducible isoform of NO synthase, on rat colonic microvascular injury provoked by Escherichia coli endotoxin (3 mg/kg i.v.) has been compared to those of aminoguanidine (25-50 mg/kg, s.c.), N(G)-iminoethyl-L-ornithine (L-NIO, 15-30 mg/kg, s.c.) and N(G)-nitro-L-arginine methyl ester (L-NAME, 2-5 mg/kg, s.c.). Administration of aminoguanidine, L-NIO or L-NAME concurrently with endotoxin provoked microvascular albumin leakage 1 h later, presumably by inhibiting constitutive NO synthase, whereas 1400W (0.1-10 mg/kg, s.c.) had no such effect. Administration of all these agents during the expression of inducible NO synthase (i.e. 3 h after endotoxin challenge) attenuated the subsequent endotoxin-provoked albumin leakage 1 h later. Moreover, concurrent administration of 1400W (0.2-5 mg/kg, s.c.; doses that did not affect systemic arterial blood pressure) with endotoxin suppressed the subsequent rise in albumin leakage after 5 h. These findings indicate that 1400W is a potent inhibitor of colonic microvascular injury associated with induction of NO synthase in vivo. 1400W will thus be useful to investigate in vivo the therapeutic potential of a selective inducible NO synthase inhibitor in inflammation.

Original languageEnglish
Pages (from-to)99-102
Number of pages4
JournalEuropean Journal of Pharmacology
Volume334
Issue number1
DOIs
Publication statusPublished - Sep 3 1997

Fingerprint

Endotoxins
Nitric Oxide Synthase
Blood Vessels
NG-Nitroarginine Methyl Ester
Protein Isoforms
Colon
Nitric Oxide Synthase Type II
Albumins
Ornithine
Wounds and Injuries
Arterial Pressure
Inflammation
pimagedine
N(G)-iminoethylornithine
Therapeutics

Keywords

  • endotoxin
  • Inducible nitric oxide (NO) synthase
  • Inflammation
  • Microcirculation
  • Nitric oxide (NO)
  • Nitric oxide (NO) synthase inhibitors
  • Vascular permeability

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Actions of isoform-selective and non-selective nitric oxide synthase inhibitors on endotoxin-induced vascular leakage in rat colon. / László, F.; Whittle, Brendan J R.

In: European Journal of Pharmacology, Vol. 334, No. 1, 03.09.1997, p. 99-102.

Research output: Contribution to journalArticle

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