Ventilatory responses during and following exposure to a hypoxic challenge in conscious mice deficient or null in S-nitrosoglutathione reductase

Lisa A Palmer; Walter J May; Kimberly deRonde; Kathleen Brown-Steinke; James N Bates; Benjamin Gaston; Stephen J Lewis

doi:10.1016/j.resp.2012.11.009

Back

Ventilatory responses during and following exposure to a hypoxic challenge in conscious mice deficient or null in S-nitrosoglutathione reductase

Journal article

Peer reviewed

Ventilatory responses during and following exposure to a hypoxic challenge in conscious mice deficient or null in S-nitrosoglutathione reductase

Lisa A Palmer, Walter J May, Kimberly deRonde, Kathleen Brown-Steinke, James N Bates, Benjamin Gaston and Stephen J Lewis

Respiratory physiology & neurobiology, Vol.185(3), pp.571-581

02/01/2013

DOI: 10.1016/j.resp.2012.11.009

PMCID: PMC3593598

PMID: 23183419

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/3593598View

Open Access

Abstract

► Initial ventilatory responses to hypoxic challenge were similar in WT and GSNOR deficient mice. ► Ventilatory roll-off occurred during hypoxic challenge in WT but not in GSNOR deficient mice. ► Post-hypoxia responses were greater in female GSNOR deficient mice than in female WT mice. Exposure to a hypoxic challenge increases ventilation in wild-type (WT) mice that diminish during the challenge (roll-off) whereas return to room air causes an increase in ventilation (short-term facilitation, STF). Since plasma and tissue levels of ventilatory excitant S-nitrosothiols such as S-nitrosoglutathione (GSNO) increase during hypoxia, this study examined whether (1) the initial increase in ventilation is due to generation of GSNO, (2) roll-off is due to increased activity of the GSNO degrading enzyme, GSNO reductase (GSNOR), and (3) STF is limited by GSNOR activity. Initial ventilatory responses to hypoxic challenge (10% O2, 90% N2) were similar in WT, GSNO+/− and GSNO−/− mice. These responses diminished markedly during hypoxic challenge in WT mice whereas there was minimal roll-off in GSNOR+/− and GSNOR−/− mice. Finally, STF was greater in GSNOR+/− and GSNOR−/− mice than in WT mice (especially females). This study suggests that GSNOR degradation of GSNO is a vital step in the expression of ventilatory roll-off and that GSNOR suppresses STF.

S-nitrosoglutathione reductase

Hypoxia

Mice

S-nitrosothiols

Ventilatory responses

Details

Title: Subtitle: Ventilatory responses during and following exposure to a hypoxic challenge in conscious mice deficient or null in S-nitrosoglutathione reductase
Creators: Lisa A Palmer - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Walter J May - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Kimberly deRonde - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Kathleen Brown-Steinke - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
James N Bates - Department of Anesthesia, University of Iowa College of Medicine, Iowa City, IA 52240, USA
Benjamin Gaston - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Stephen J Lewis - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Resource Type: Journal article
Publication Details: Respiratory physiology & neurobiology, Vol.185(3), pp.571-581
DOI: 10.1016/j.resp.2012.11.009
PMID: 23183419
PMCID: PMC3593598
NLM abbreviation: Respir Physiol Neurobiol
ISSN: 1569-9048
eISSN: 1878-1519
Publisher: Elsevier B.V
Grant note: name: NIH Program Project Grant, award: 1P01HL101871; DOI: 10.13039/100000005, name: Department of Defense, award: W81XWH-07-0134; name: Galleon Pharmaceuticals; name: NIH, award: R01 HL59337
Language: English
Date published: 02/01/2013
Academic Unit: Anesthesia
Record Identifier: 9984006484002771

Metrics

22 Record Views

31 Times Cited - Web of Science