Premium
Sympathetic perivascular nerves contribute to hypoxic transformation of smooth muscle phenotype in ovine cerebral arteries
Author(s) -
Adeoye Olayemi O,
Silpanisong Jinjutha,
Williams James M,
Pearce William J
Publication year - 2013
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.27.1_supplement.700.4
Subject(s) - colocalization , cerebral arteries , endocrinology , medicine , hypoxia (environmental) , biology , tyrosine hydroxylase , sympathectomy , anatomy , chemistry , dopamine , microbiology and biotechnology , organic chemistry , oxygen
In addition to its role in angiogenesis, VEGF may also contribute to arterial remodeling, possibly through activation of VEGF receptors on sympathetic nerves leading to altered trophic input to the arterial wall. To test this hypothesis normoxic and chronically hypoxic fetal sheep (110 days at 3820m) underwent unilateral superior cervical sympathectomy (SANX) at 124d gestation, and then were harvested at 138d (term). In middle cerebral arteries (MCA), hypoxia increased dopamine beta hydroxylase 360% and SANX ablated this increase. Hypoxia also decreased by 34% colocalization between Non‐Muscle Myosin Heavy Chain (MHC) and smooth muscle α‐actin (AA) indicating increased contractile differentiation; SANX increased this colocalization 106%. Conversely, hypoxia increased by 124% SM2‐MHC colocalization with AA, again indicating increased differentiation; SANX decreased this colocalization by 81%. Organ culture of MCA with NE decreased colocalization of SM2‐MHC with AA by 88% in intact arteries, but increased it 62% in SANX arteries; all effects of NE were blocked by prazosin. These results suggest that hypoxic increases in VEGF alter sympathetic release of NE and/or other factors that transform the contractile phenotype of cerebrovascular smooth muscle. This transformation appears to be a central feature of hypoxic cerebrovascular remodeling in the fetus. Supported by PHS# P01‐HD31226.