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Upregulation of Orexin Receptor 1 Contributes to Increased Sympathetic Output in Obese Zucker Rats
Author(s) -
Li De-Pei,
Pan Hui-Lin
Publication year - 2012
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.26.1_supplement.705.9
Subject(s) - medicine , endocrinology , orexin , microinjection , spinal cord , chemistry , baroreflex , orexin a , glutamatergic , hypothalamus , orexin receptor , receptor , biology , glutamate receptor , blood pressure , neuroscience , neuropeptide , heart rate
Increased sympathetic outflow is involved in the pathogenesis of metabolic syndrome. Orexins are important in the control of autonomic function and energy metabolism. We determined the role of orexins in the control of the paraventricular (PVN) presympathetic neurons in Obese Zucker Rats (OZRs) and Lean Zucker Rats (LZRs). The PVN‐spinal cord output neurons were retrogradely labeled by fluorescent microspheres injected into the rat thoracic spinal cord. The basal firing rate in the labeled PVN neurons was higher in OZRs than in LZRs. Orexin A produced a greater dose‐dependent increase in the firing rate in PVN neurons in OZRs than in LZRs. Orexin A caused a greater increase in NMDA currents induced by puff application of NMDA in OZRs than in LZRs. Orexin A increased the frequency of spontaneous excitatory postsynaptic currents in labeled PVN neurons. The orexin receptor 1 (OX1R) expression level in the PVN was higher in OZRs than in LZRs. OX1R immunoreactivity was colocalized with microsphere‐labeled PVN‐spinal neurons. In addition, microinjection of orexin A into the PVN produced greater increases in arterial blood pressure (ABP) and lumbar sympathetic nerve activity (LSNA) in anesthetized OZRs than in LZRs. Collectively, these data suggest that upregulated OX1R in the PVN contributes to increased sympathetic outflow and hyperactivity of PVN presympathetic neurons through enhancing glutamatergic transmission.