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NPY ő a regulator of hypoxic cerebrovascular remodeling in fetal lambs (853.4)
Author(s) -
Latschaw Kimberly,
Adeoye Olayemi,
Silpanisong Jinjutha,
Kim Dahlim,
Williams James,
Pearce William
Publication year - 2014
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.28.1_supplement.853.4
Subject(s) - guanethidine , medicine , endocrinology , fetus , hypoxia (environmental) , cerebral arteries , receptor , sympathectomy , stimulation , chemistry , biology , pregnancy , organic chemistry , oxygen , genetics
Prenatal, intra‐partum or post partum exposure of a fetus to hypoxia results in structural and functional changes in cerebral arteries, known as remodeling. Sympathetic nerves have been suggested to contribute to this process. Whereas NE is suggested as the major mediator of adrenergic effects, our preliminary experiments show that there is a guanethidine‐resistant (norepinephrine‐independent) component. This study explores the hypothesis that NPY contributes to hypoxic cerebrovascular remodeling in the fetal cerebral circulation. Chronic hypoxia (CH) produced a 254% ↑ in K‐induced tone and a 30% ↓ in stretch‐induced myogenic tone in fresh nerve‐intact fetal cerebral arteries. CH also increased the magnitude of nerve stimulation induced guanethidine‐resistant contractile tone. Immunohistochemistry revealed that CH significantly ↑ cerebrovascular NPY whereas sympathectomy (SANX) ablated this effect. Likewise, Western blot quantification of NPY‐Y1 receptors revealed that CH increased Y1 receptors 73%. Whereas SANX in normoxic tissues had no significant effect, SANX produced a 30% ↓ in Y1 receptors in hypoxic arteries. Together these results suggest that NPY released from sympathetic cerebrovascular nerves contributes to hypoxic remodeling through increased NPY content/release and Y1 receptor density. Grant Funding Source : Supported by NIH Grants HD‐31266 and NS‐076945