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Vascular Endothelial Growth Factor (VEGF A ) induced phrenic motor facilitation (PMF) requires ERK activation
Author(s) -
DaleNagle Erica Arden,
Mitchell Gordon S
Publication year - 2009
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.23.1_supplement.607.6
Subject(s) - mapk/erk pathway , vascular endothelial growth factor , angiogenesis , medicine , vegf receptors , endocrinology , chemistry , kinase , pharmacology , biochemistry
VEGF A is a hypoxia‐induced growth factor known to regulate angiogenesis. We recently demonstrated that VEGF A is expressed in presumptive phrenic motor neurons (Dale et al., FASEB J ., 2007) and that cervical spinal VEGF A receptor activation elicits long‐lasting PMF (Dale‐Nagle and Mitchell, FASEB J. , 2008). Since VEGF receptor 2 signals via ERK 1/2 MAP kinase, we tested the hypothesis that ERK 1/2 activation is necessary for VEGF A ‐induced PMF. Anesthetized, pump‐ventilated, paralyzed and vagotomized male, Sprague‐Dawley rats were prepared with two intrathecal catheters at C4. Recordings of integrated phrenic nerve activity were made with three groups after intrathecal injections of: 1) vehicle (10μL of 0.1% BSA in aCSF; n=6); 2) VEGF A (100ng; n=6); or 3) U0126 (100μM, 12μL; n=3), a MEK1/2 inhibitor, 30 min prior to VEGF A . VEGF A induced PMF for at least 90 min post‐injection (59% ± 7% baseline; p<0.01), an effect significantly greater (p<0.01) than in rats pretreated with U0126 (16% ± 8%; n.s.) or time controls (9% ± 8%; n.s.). Our results provide the first evidence that VEGF A elicits spinal synaptic plasticity by a mechanism requiring ERK 1/2 MAP kinase activation. Supported by NIH NS05777 & HL80209 .