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Chronic hypoxia modulates effects of VEGF receptors on structure and function in ovine common carotid arteries
Author(s) -
Hubbell Margaret C,
Butler Stacy M,
Abrassart Jenna M,
Semotiuk Andrew M,
Williams James M,
Pearce William J
Publication year - 2011
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.25.1_supplement.1091.16
Subject(s) - hypoxia (environmental) , medicine , endocrinology , contraction (grammar) , receptor , antagonist , kinase insert domain receptor , phenotype , vascular smooth muscle , chemistry , biology , vegf receptors , vascular endothelial growth factor , smooth muscle , vascular endothelial growth factor a , oxygen , biochemistry , gene , organic chemistry
To elucidate mechanisms whereby chronic hypoxia alters arterial structure and function, we explored the hypothesis that hypoxia influences the ability of VEGF to modulate smooth muscle phenotype in ovine carotid arteries. Endothelium‐denuded common carotid arteries from non‐pregnant adult sheep maintained at either sea level (N) or 3280 m for 110 days (H) were studied after 24h of serum starvation followed by 24h of treatment with: 1) serum starvation (S); 2) 3 ng/ml VEGF; or 3) 160 pM VEGF + 240 nM vatalanib. VEGF treatment differentially affected medial thickness (N: +13%; H: −5%), K+ induced contraction (N: −66%; H:+36%), and myogenic contraction (N: −66%; H: −37%). These responses to low physiological levels of VEGF were reversed by treatment with vatalanib, a mixed VEGF receptor antagonist. Together, these data support the hypothesis that chronic hypoxia modulates the coupling between VEGF receptor activation on contractile protein expression and smooth muscle phenotype in ovine carotid arteries. Supported by PHS grant# P01‐HD31226