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Neural programming of vascular maturation and effects of denervation (1079.13)
Author(s) -
Reho John,
Zheng Xiaoxu,
Benjamin James,
Fisher Steven
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.1079.13
Subject(s) - denervation , vascular smooth muscle , endocrinology , sympathectomy , medicine , adventitia , biology , anatomy , smooth muscle
From birth through maturity the blood pressure in humans and animals steadily increases yet the basis of vascular maturation is unknown. The sympathetic nervous system innervates the mesenteric arterial tree post‐natally. We hypothesized that neural inputs program post‐natal maturation of regional circulations vascular smooth muscle (VSM). Chemical sympathectomy was achieved via 6‐hydroxydopamine initiated at PND1. Denervation in adult rats was achieved via disruption of the renal artery adventitia followed by a 10% phenol solution. Rat MA VSM matures from PND 12‐35 as evidenced by 1) 10‐50 fold induction of contractile protein expression via qPCR, including CPI‐17 2) 25‐50 fold induction of the α1‐adrenergic (Adra1), purinergic (P2RX1) and NPY (NPY1R) receptors that mediate VSM neural responses 3) switching of myosin phosphatase splice variant isoforms from E24‐ (LZ+) to E24+ (LZ‐). Denervation during development or in adults caused a reversion to a more immature VSM gene program. Vascular contractility via wire myography paralleled the changes in gene expression, with increased calcium sensitization during development that was inhibited by denervation. We propose that sympathetic neural inputs developmentally program MA VSM to capture control of vascular function in a feed forward manner. Removal of neural inputs programming VSM may contribute to the salutary effects of denervation in hypertension. Grant Funding Source : HL066171