title: Neuropeptide Y acts in the paraventricular nucleus to suppress sympathetic nerve activity and its baroreflex regulation.
abstract: Neuropeptide Y (NPY), a brain neuromodulator that has been strongly implicated in the regulation of energy balance, also acts centrally to inhibit sympathetic nerve activity (SNA); however, the site and mechanism of action are unknown. In chloralose-anaesthetized female rats, nanoinjection of NPY into the paraventricular nucleus of the hypothalamus (PVN) dose-dependently suppressed lumbar SNA (LSNA) and its baroreflex regulation, and these effects were blocked by prior inhibition of NPY Y1 or Y5 receptors. Moreover, PVN injection of Y1 and Y5 receptor antagonists in otherwise untreated rats increased basal and baroreflex control of LSNA, indicating that endogenous NPY tonically inhibits PVN presympathetic neurons. The sympathoexcitation following blockade of PVN NPY inhibition was eliminated by prior PVN nanoinjection of the melanocortin 3/4 receptor inhibitor SHU9119. Moreover, presympathetic neurons, identified immunohistochemically using cholera toxin b neuronal tract tracing from the rostral ventrolateral medulla (RVLM), express NPY Y1 receptor immunoreactivity, and patch-clamp recordings revealed that both NPY and α-melanocyte-stimulating hormone (α-MSH) inhibit and stimulate, respectively, PVN-RVLM neurons. Collectively, these data suggest that PVN NPY inputs converge with α-MSH to influence presympathetic neurons. Together these results identify endogenous NPY as a novel and potent inhibitory neuromodulator within the PVN that may contribute to changes in SNA that occur in states associated with altered energy balance, such as obesity and pregnancy.
authors.affiliation: Oregon Health & Science University, Department of Physiology and Pharmacology, 1381 SW Sam Jackson Park Rd - L334, Portland, OR 97239, USA.  brooksv@ohsu.edu.
authors.forename: Priscila A
authors.initials: PA
authors.lastname: Cassaglia
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Shi
authors.forename: Baoxin
authors.initials: B
authors.lastname: Li
authors.forename: Wagner L
authors.initials: WL
authors.lastname: Reis
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Clute-Reinig
authors.forename: Javier E
authors.initials: JE
authors.lastname: Stern
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Brooks
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials; D005260:Female; D007267:Injections; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C100568:neuropeptide Y5 receptor; D000521:alpha-MSH