title: Ventilatory responses during and following exposure to a hypoxic challenge in conscious mice deficient or null in S-nitrosoglutathione reductase.
abstract: 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% O(2), 90% N(2)) 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.
authors.affiliation: Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Palmer
authors.forename: Walter J
authors.initials: WJ
authors.lastname: May
authors.forename: Kimberly
authors.initials: K
authors.lastname: deRonde
authors.forename: Kathleen
authors.initials: K
authors.lastname: Brown-Steinke
authors.forename: James N
authors.initials: JN
authors.lastname: Bates
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lewis
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003243:Consciousness; D005260:Female; D000860:Hypoxia / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012123:Pulmonary Ventilation / Q000502:physiology*
chemical_list: D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent