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Upregulation of Orexin Receptor in Paraventricular Nucleus Promotes Sympathetic Outflow Through Non‐selective Cation Channel in Obesity
Author(s) -
Zhou JingJing,
Chen ShaoRui,
Yuan Fang,
Zhang Yi,
Li DePei
Publication year - 2015
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.29.1_supplement.647.5
Subject(s) - orexin , orexin receptor , medicine , endocrinology , orexin a , hypothalamus , microinjection , nucleus , receptor , chemistry , neuropeptide , biology , neuroscience
Elevated sympathetic outflow contributes to hypertension in obesity. Orexins importantly regulates autonomic function. Presently we determined the role of orexin in the paraventricular (PVN) nucleus of hypothalamus in controlling sympathetic outflow in obese Zucker rats (OZRs) and lean Zucker rats (LZRs). Orexin A microinjection into PVN significiantly dose‐dependently elevated arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) manner in anesthetized OZRs than LZRs, which eliminated by SB‐334867, orexin receptor 1 receptor (OX1R) antagonist, but not TCS‐OX2‐29, OX2R antagonist. Furthermore, SB‐334867 reduced basal ABP and RSNA in OZRs but not LZRs. Compared with LZRs, OX1R expression in PVN was significantly higher in OZRs, while no difference for OX2R. OX1R immunoreactivity was positive in retrogradely labeled PVN‐spinal neurons. Compared with LZRs, the basal firing rate in the PVN‐spinal neurons was higher in OZRs, and orexin A excited firing activity in PVN‐spinal neurons in OZRs, which eliminated by SB334867. SB334867 also decreased basal firing activity of these neurons in OZRs. In addition, orexin A induced larger currents in PVN spinal neurons in OZRs. These data suggest that upregulation of OX1R in the PVN promotes hyperactivity of PVN presympathetic neurons and sympathetic outflow in obesity. This work was supported by National Institutes of Health (Grants MH096086 to D.‐P. L.) and National Natural Sciences Foundation of China (31271223 and 31071002).