Endothelium-dependent vasodilation in response to Pseudomonas aeruginosa lipopolysaccharide: An in vitro study on canine arteries

P. R.B. Evora, S. Ekin, P. J. Pearson, H. V. Schaff

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Early systemic arterial hypotension is a common clinical feature of Pseudomonas septicemia. To determine if Pseudomonas aeruginosa endotoxin induces the release of endothelium-derived nitric oxide (EDNO), an endogenous nitrovasodilator, segments of canine femoral, renal, hepatic, superior mesenteric, and left circumflex coronary arteries were suspended in organ chambers (physiological salt solution, 95% O2/5% CO2, pH 7.4, 37°C) to measure isometric force. In arterial segments contracted with 2 μM prostaglandin F(2α), Pseudomonas endotoxin (lipopolysaccharide (LPS) serotype 10(Habs) from Pseudomonas aeruginosa (0.05 to 0.50 mg/ml) induced concentration-dependent relaxation of segments with endothelium (P < 0.05) but no significant change in tension of arteries without endothelium. Endothelium-dependent relaxation in response to Pseudomonas LPS occurred in the presence of 1 μM indomethacin, but could be blocked in the coronary artery with 10 μM N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthesis from L-arginine. The inhibitory effect of L-NMMA on LPS-mediated vasorelaxation of the coronary artery could be reversed by exogenous 100 μM L-arginine but not by 100 μM D-arginine. These experiments indicate that Pseudomonas endotoxin induces synthesis of nitric oxide from L-arginine by the vascular endothelium. LPS-mediated production of EDNO by the endothelium, possibly through the action of constitutive nitric oxide synthase (NOSc), may decrease systemic vascular resistance and may be the mechanism of early hypotension characteristic of Pseudomonas septicemia.

Original languageEnglish (US)
Pages (from-to)1329-1334
Number of pages6
JournalBrazilian Journal of Medical and Biological Research
Volume31
Issue number10
DOIs
StatePublished - Oct 1998

Keywords

  • EDRF
  • Endothelium-derived relaxing factor
  • Hypotension
  • Nitric oxide
  • Sepsis

ASJC Scopus subject areas

  • Biophysics
  • Neuroscience(all)
  • Biochemistry
  • Physiology
  • Immunology
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Cell Biology

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