Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Neuroendocrinology DOI: 10.1159/000188602 Stress-Induced Hypertension and Increased Sympathetic Activity in Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons Suvi T. Ruohonen a, c Eriika Savontaus a, d Petteri Rinne a, c Joana Rosmaninho-Salgado b Claudia Cavadas b Heikki Ruskoaho e Markku Koulu a Ullamari Pesonen a a Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland; b Center of Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; c Drug Discovery Graduate School, University of Turku, and d Clinical Pharmacology, TYKSLAB, Health Care District of Southwest Finland, Turku, and e Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland NPY DBH mice. Blood pressure during surgical stress was sig- nificantly increased in comparison with wild-type controls. Furthermore, OE-NPY DBH mice showed sexually dimorphic NPY responses to stress, and an anxiolytic-like behavior in elevated plus-maze and light-dark tests. Conclusion: This study shows that the overactive noradrenergic NPY system plays a role in regulation of blood pressure and adaptive re- sponses to stress, and may be a link between chronic stress and adiposity-associated disturbances in metabolism. Copyright © 2008 S. Karger AG, Basel Introduction Neuropeptide Y (NPY), a 36-amino acid neurotrans- mitter, is one of the most abundant peptides in the mam- malian nervous system, and contributes to diverse endo- crinologic and behavioral functions both centrally and peripherally. NPY is also a transmitter of the sympathet- ic nervous system (SNS), where it is colocalized with adrenaline and noradrenaline (NA) in adrenergic and noradrenergic neurons. The release of these neurotrans- mitters from the sympatho-adrenomedullary system to the circulation is synchronized during sympathetic acti- Key Words Transgenic mouse model  Sympathetic nervous system  Adrenal gland  Corticosterone Abstract Background and Aims: Neuropeptide Y (NPY) is a sympa- thetic neurotransmitter co-stored and co-released with nor- adrenaline and adrenaline. We have constructed a novel NPY transgenic mouse model (OE-NPY DBH mouse) where target- ed overexpression results in increased levels of NPY in the brainstem and adrenal glands. The present study was aimed to understand the role of NPY released from sympathetic nerves and brain noradrenergic neurons in regulation of blood pressure, and behavioral responses to stress. Meth- ods: Blood pressure was measured by radiotelemetry in conscious male OE-NPY DBH and wild-type mice during surgi- cal stress and in baseline conditions. Plasma and adrenal gland catecholamine levels were measured at baseline. Acute immobilization and cold exposure were used to study the plasma levels of NPY and corticosterone in stress, and brown adipose tissue thermogenic activity was measured with [ 3 H]GDP binding after cold. Results: Here, we demon- strate that sympathoadrenal activity is enhanced in the OE- Received: August 25, 2008 Accepted after revision: October 9, 2008 Published online: December 20, 2008 Ullamari Pesonen Department of Pharmacology, Drug Development and Therapeutics University of Turku FI–20014 Turun yliopisto (Finland) Tel. +358 50 966 7967, Fax +358 2 333 7216, E-Mail ullamari.pesonen@utu.fi © 2008 S. Karger AG, Basel 0028–3835/09/0000–0000$26.00/0 Accessible online at: www.karger.com/nen