title: Paraventricular nucleus corticotrophin releasing hormone contributes to sympathoexcitation via interaction with neurotransmitters in heart failure.
abstract: Recent studies indicate that systemic administration of tumor necrosis factor (TNF)-α induces increases in corticotrophin releasing hormone (CRH) and CRH type 1 receptors in the hypothalamic paraventricular nucleus (PVN). In this study, we explored the hypothesis that CRH in the PVN contributes to sympathoexcitation via interaction with neurotransmitters in heart failure (HF). Sprague-Dawley rats with HF or sham-operated controls (SHAM) were treated for 4 weeks with a continuous bilateral PVN infusion of the selective CRH-R1 antagonist NBI-27914 or vehicle. Rats with HF had higher levels of glutamate, norepinephrine (NE) and tyrosine hydroxylase (TH), and lower levels of gamma-aminobutyric acid (GABA) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN when compared to SHAM rats. Plasma levels of cytokines, NE, ACTH and renal sympathetic nerve activity (RSNA) were increased in HF rats. Bilateral PVN infusions of NBI-27914 attenuated the decreases in PVN GABA and GAD67, and the increases in RSNA, ACTH and PVN glutamate, NE and TH observed in HF rats. These findings suggest that CRH in the PVN modulates neurotransmitters and contributes to sympathoexcitation in rats with ischemia-induced HF.
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, China. ykang@mail.xjtu.edu.cn
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Kang
authors.forename: Ai-Qun
authors.initials: AQ
authors.lastname: Zhang
authors.forename: Xiu-Fang
authors.initials: XF
authors.lastname: Zhao
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Cardinale
authors.forename: Carrie
authors.initials: C
authors.lastname: Elks
authors.forename: Xi-Mei
authors.initials: XM
authors.lastname: Cao
authors.forename: Zhen-Wen
authors.initials: ZW
authors.lastname: Zhang
authors.forename: Joseph
authors.initials: J
authors.lastname: Francis
mesh_terms: D000814:Aniline Compounds / Q000008:administration & dosage; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D042282:Microdissection; D018377:Neurotransmitter Agents / Q000032:analysis / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D011743:Pyrimidines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
chemical_list: C471210:2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine; D000814:Aniline Compounds; D018377:Neurotransmitter Agents; D011743:Pyrimidines; D003346:Corticotropin-Releasing Hormone