Contribution of peroxynitrite to fatal cardiovascular depression induced by overproduction of nitric oxide in rostral ventrolateral medulla of the rat

S. H.H. Chan, L. L. Wang, C. C. Ou, J. Y.H. Chan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

30 Scopus citations

Abstract

We evaluated the contribution of peroxynitrite to the fatal cardiovascular depression induced by overproduction of nitric oxide (NO) after activation of inducible NO synthase (iNOS) in the rostral ventrolateral medulla (RVLM), the origin of sympathetic vasomotor tone. In Sprague-Dawley rats maintained under propofol anesthesia, microinjection of E. coli lipopolysaccharide (LPS) bilaterally into the RVLM elicited significant hypotension, bradycardia, reduction in sympathetic vasomotor tone and mortality. There was also a discernible elevation of iNOS expression in the ventrolateral medulla, followed by a massive production of nitrotyrosine, an experimental index for peroxynitrite. Co-administration bilaterally into the RVLM of the selective iNOS inhibitor, S-methylisothiourea (50, 100 or 250 pmol), an active peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis- (N-methyl-4′-pyridyl)-porphyrinato iron (III) (10 or 50 pmol), a peroxynitrite scavenger, L-cysteine (5, 50 or 100 pmol), or a superoxide dismutase mimetic, Mn(III)-tetrakis-(4-benzoic acid) porphyrin (1 or 10 pmol), significantly prevented mortality, reduced nitrotyrosine production and reversed the NO-induced cardiovascular suppression after application of LPS into the RVLM. We conclude that the formation of peroxynitrite by a reaction between superoxide anion and NO is primarily responsible for the fatal cardiovascular depression induced by overproduction of NO after activation of iNOS at the RVLM.

Original languageEnglish
Pages (from-to)889-898
Number of pages10
JournalNeuropharmacology
Volume43
Issue number5
DOIs
StatePublished - 10 2002
Externally publishedYes

Keywords

  • Cardiovascular depression
  • Fatality
  • Inducible nitric oxide synthase
  • Nitric oxide
  • Peroxynitrite
  • Rostral ventrolateral medulla
  • Superoxide anion

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