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Spinal VEGF induced phrenic motor facilitation is unaffected by pretreatment with repetitive acute intermittent hypoxia
Author(s) -
Dale Erica Arden,
Satriotomo Irawan,
Mitchell Gordon S
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.704.10
Subject(s) - phrenic nerve , intermittent hypoxia , hypoxia (environmental) , medicine , endocrinology , receptor , vegf receptors , vascular endothelial growth factor , downregulation and upregulation , anesthesia , respiratory system , chemistry , oxygen , biochemistry , gene , organic chemistry , obstructive sleep apnea
Vascular endothelial growth factor (VEGF) and VEGF receptor‐2 (VEGFR‐2) are expressed in identified phrenic motor neurons, and cervical spinal VEGF receptor activation elicits long‐lasting phrenic motor facilitation (pMF), demonstrating the potential of VEGFA to elicit respiratory plasticity. Since VEGF and VEGFR‐2 are regulated by hypoxia, we tested the hypotheses that: 1) VEGF and VEGFR‐2 are upregulated in phrenic motor neurons after repetitive exposure to acute intermittent hypoxia (3× per wk, 10 wks; 3xwAIH); and 2) 3xwAIH (4 wks) enhances VEGF‐induced pMF due to VEGF receptor up‐regulation. 3xwAIH increases VEGF (2.9±0.2 vs. 1.0±0.3; p<0.05) and VEGFR‐2 expression vs normoxic controls (8.7±0.07 vs. 1.9±0.5; p<0.05). Cervical spinal VEGFA administration elicited similar pMF in normoxic and 3xwAIH treated rats. Thus, although repetitive intermittent hypoxia up‐regulates VEGF and VEGR‐R expression in phrenic motor neurons, there was no evidence for any functional effect. Further exploration of this issue is warranted since: 1) there may be a “ceiling effect” as VEGF‐induced pMF may elicit maximal phrenic output, or 2) 4 weeks of 3xwAIH may not be sufficient time to up‐regulate the relevant proteins. Supported by: NIH NS05777 & HL080209.