Effect of nitrite on endothelial function in isolated lung

I. C. Ehrhart, L. Zou, M. J. Theodorakis, J. B. Parkerson, X. Gu, Ruth B Caldwell, J. D. Catravas

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Nitrated tyrosine, implicated in protein dysfunction, is increased in various tissues in association with diverse pathological processes. Angiotensin converting enzyme (ACE) is a luminal vascular endothelial enzyme whose dysfunction is an early sign of endothelial injury. ACE contains a tyrosine critical for its enzymatic activity. Others have shown that nitrite exacerbates the ACE dysfunction of cultured endothelial cells in contact with activated polymorphonuclear neutrophils (PMN). We hypothesized that exogenous nitrite would enhance endothelial ACE dysfunction associated with PMN activation in the isolated lung. Rats received lipopolysaccharide (LPS) 2 h prior to isolated lung perfusion with Ficoll containing buffer. Either formyl-Met-Leu-Phe (fMLP, 10-7 M) or phorbol myristate acetate (PMA, 10-7 M) was used to activate PMN in lungs treated or not treated with 300-μM nitrite. A first pass indicator dilution method and first order reaction kinetics were used to determine ACE activity, while lung Ficoll content served as an index of vascular permeability. Both fMLP and PMA decreased endothelial ACE activity and increased pulmonary artery pressure, edema and vascular permeability. Exogenous nitrate did not potentiate the decrease in ACE activity, the lung injury or nitrotyrosine immunoreactivity of lung homogenates. In contrast to observations in cultured endothelial cells, our findings in the whole lung are compatible with the speculation of others that the rat lung has an unidentified factor, which minimizes accumulation of nitrated proteins.

Original languageEnglish (US)
Pages (from-to)401-408
Number of pages8
JournalGeneral Pharmacology: The Vascular System
Volume34
Issue number6
DOIs
StatePublished - Dec 1 2000

Keywords

  • 3-Nitrotyrosine
  • Angiotensin converting enzyme
  • Endothelial injury
  • Formyl-met-leu-phe
  • Lipopolysaccharide
  • Lung
  • Nitrite
  • Phorbol myristate acetate
  • Polymorphonuclear neutrophils
  • Rat
  • Vascular permeability

ASJC Scopus subject areas

  • Pharmacology

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