CRF, Adrenocorticotrophin, Adrenal Steroids and Stress

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<sup>a

a</sup>Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland;
^bCenter of Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal;
^cDrug Discovery Graduate School, University of Turku, and
^dClinical Pharmacology, TYKSLAB, Health Care District of Southwest Finland, Turku, and
^eDepartment of Pharmacology and Toxicology, University of Oulu, Oulu, Finland

Address of Corresponding Author

Neuroendocrinology 2009;89:351-360 (DOI: 10.1159/000188602)

  Key Words

• Transgenic mouse model
• Sympathetic nervous system
• Adrenal gland
• Corticosterone

  Abstract

Background and Aims: Neuropeptide Y (NPY) is a sympathetic neurotransmitter co-stored and co-released with noradrenaline and adrenaline. We have constructed a novel NPY transgenic mouse model (OE-NPY^DBH mouse) where targeted 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. Methods: Blood pressure was measured by radiotelemetry in conscious male OE-NPY^DBH and wild-type mice during surgical 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 [³H]GDP binding after cold. Results: Here, we demonstrate that sympathoadrenal activity is enhanced in the OE-NPY^DBH mice. Blood pressure during surgical stress was significantly 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 responses to stress, and may be a link between chronic stress and adiposity-associated disturbances in metabolism.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

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

  Article Information

Received: August 25, 2008
Accepted after revision: October 9, 2008
Published online: December 20, 2008
Number of Print Pages : 10
Number of Figures : 5, Number of Tables : 2, Number of References : 29