Attenuation by nitrosothiol NO donors of acute intestinal microvascular dysfunction in the rat

F. László, B. J.R. Whittle, S. Moncada

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The effects of the nitric oxide (NO) donors, S‐nitroso‐glutathione (SNG) and S‐nitroso‐N‐acetyl‐penicillamine (SNAP), on the acute intestinal microvascular dysfunction induced by NG‐nitro‐L‐arginine methyl ester (L‐NAME) in combination with low doses of endotoxin were investigated in the anaesthetized rat. Administration of L‐NAME (5mg kg−1, s.c.) concurrently with E. coli lipopolysaccharide (LPS, 3 mg kg−1, i.v.) provoked the leakage of radiolabelled albumin in the ileum and colon, as a measure of microvascular damage, determined 1 h after challenge. Intravenous infusion of SNOG or SNAP (1–10 μg kg−1 min−1) dose‐dependently attenuated the microvascular leakage induced by L‐NAME and LPS. Infusion of the lowest doses of SNOG or SNAP (1 μg kg−1 min−1, i.v.) that significantly reduced the albumin leakage, did not affect the increase in blood pressure in response to L‐NAME in LPS‐treated rats. Higher doses of SNOG or SNAP (5–10 μg kg−1 min−1, i.v.) dose‐dependently reduced this increase in blood pressure. In control studies, intravenous infusion of glutathione (10 μg kg−1 min−1) or N‐acetyl‐penicillamine (10 μg kg−1 min−1) had no effect on microvascular leakage in the ileum and colon induced by LPS and L‐NAME. Pretreatment with rabbit anti‐rat neutrophil serum (0.4 ml kg−1, i.p., 4h before challenge), which reduced the neutrophil count in peripheral arterial blood, also inhibited the microvascular leakage in the ileum and colon. The protective effects of the nitrosothiol NO donors in this model may reflect, in part, modulation of neutrophil interactions within the microcirculation or actions on endothelial cell integrity, in addition to any local vasodilator action. 1995 British Pharmacological Society

Original languageEnglish
Pages (from-to)498-502
Number of pages5
JournalBritish journal of pharmacology
Volume115
Issue number3
DOIs
Publication statusPublished - Jun 1995

Keywords

  • NO donors
  • NO synthase inhibitors
  • Nitric oxide
  • N‐nitro‐L‐arginine methyl ester
  • S‐nitroso‐N‐acetyl‐penicillamine
  • S‐nitroso‐glutathione
  • endothelial injury
  • intestinal inflammation
  • neutrophils
  • nitrosothiols
  • rat intestinal vasculature

ASJC Scopus subject areas

  • Pharmacology

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