S-Nitrosothiols signal the ventilatory response to hypoxia

Andrew J. Lipton, Michael A. Johnson, Timothy Macdonald, Michael W. Lieberman, David Gozal, Benjamin Gaston

Research output: Contribution to journalArticle

261 Scopus citations

Abstract

Increased ventilation in response to hypoxia has been appreciated for over a century1, but the biochemistry underlying this response remains poorly understood. Here we define a pathway in which increased minute ventilation (V̇E) is signalled by deoxyhaemoglobin -derived S-nitrosothiols (SNOs). Specifically, we demonstrate that S-nitrosocysteinyl glycine (CGSNO) and S-nitroso-Lcysteine (L-CSNO) - - (D-CSNO)-reproduce the ventilatory effects of hypoxia at the level of the nucleus tractus solitarius (NTS). We show that plasma from deoxygenated, but not from oxygenated, blood produces the ventilatory effect of both SNOs and hypoxia. Further, this activity is mediated by S-nitrosoglutathione (GSNO), and GSNO activation by γ-glutamyl transpeptidase (γ-GT) is required. The normal response to hypoxia is impaired in a knockout mouse lacking γGT. These observations suggest that S-nitrosothiol biochemistry is of central importance to the regulation of breathing.

Original languageEnglish (US)
Pages (from-to)171-174
Number of pages4
JournalNature
Volume413
Issue number6852
DOIs
StatePublished - Sep 13 2001

ASJC Scopus subject areas

  • General

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