Stress-induced hypertension and increased sympathetic activity in mice overexpressing neuropeptide Y in noradrenergic neurons.
OBJECTIVE
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 [(3)H]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.


CONCLUSIONS
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.
Ruohonen
Suvi T
ST
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
Savontaus
Eriika
E
Rinne
Petteri
P
Rosmaninho-Salgado
Joana
J
Cavadas
Claudia
C
Ruskoaho
Heikki
H
Koulu
Markku
M
Pesonen
Ullamari
U
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004837:Epinephrine / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D012737:Sex Factors; D013312:Stress, Physiological
D009478:Neuropeptide Y; D006153:Guanosine Diphosphate; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine