Endotoxin triggers the expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in the rat aorta in vivo

Csaba Szabo, Andrew L. Salzman, Harry Ischiropoulos

Research output: Contribution to journalArticle

227 Citations (Scopus)

Abstract

The free radicals nitric oxide (·NO) and superoxide (O2 -) are known to react to form peroxynitrite (ONOO-), a highly reactive species. Peroxynitrite has been suggested to play an important role in the cellular damage associated with the overproduction of ·NO, but there are very limited data regarding its in vivo formation. Here we demonstrate that injection of endotoxin into rats leads to the expression of an inducible isoform of ·NO synthase (iNOS) in the thoracic aorta at 6 h and an increase in the circulating levels of nitrite/nitrate. Moreover, at the same time point, there is a marked increase in the immunoreactivity of nitrotyrosine, a marker of peroxynitrite in the aorta. The formation of nitrotyrosine was prevented by inhibiting the activity of NOS by NG-methyl-l-arginine in vivo. Our data suggest that during endotoxin shock, part of ·NO, produced following the induction of iNOS, is converted into peroxynitrite in the vicinity of large blood vessels. The demonstration of the in vivo formation of peroxynitrite at sites of ·NO overproduction may necessitate the development of novel and additional approaches for limiting or preventing ·NO-related cytotoxic or vasodilatory actions during circulatory shock.

Original languageEnglish (US)
Pages (from-to)235-238
Number of pages4
JournalFEBS Letters
Volume363
Issue number3
DOIs
StatePublished - Apr 24 1995
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Nitric Oxide Synthase Type II
Endotoxins
Nitric Oxide Synthase
Aorta
Rats
Nitric Oxide
Protein Isoforms
Shock
Blood vessels
Nitrites
Thoracic Aorta
Superoxides
Nitrates
Free Radicals
Blood Vessels
Arginine
Demonstrations
Injections

Keywords

  • Contraction
  • Immunohistochemistry
  • Nitric oxide
  • Nitrotyrosine
  • Peroxynitrite
  • Septic shock
  • Superoxide

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

Endotoxin triggers the expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in the rat aorta in vivo. / Szabo, Csaba; Salzman, Andrew L.; Ischiropoulos, Harry.

In: FEBS Letters, Vol. 363, No. 3, 24.04.1995, p. 235-238.

Research output: Contribution to journalArticle

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