title: Orexin neuron-mediated skeletal muscle vasodilation and shift of baroreflex during defense response in mice.
abstract: We have previously shown that some features of the defense response, such as increases in arterial blood pressure (AP), heart rate (HR), and ventilation were attenuated in prepro-orexin knockout (ORX-KO) mice. Here, we examined whether the same was true in orexin neuron-ablated [orexin/ataxin-3 transgenic mice (ORX/ATX-Tg)] mice. In addition, we examined other features of the defense response: skeletal muscular vasodilation and shift of baroreceptor reflex. In both anesthetized and conscious conditions, basal AP in ORX/ATX-Tg mice was significantly lower by approximately 20 mmHg than in wild-type (WT) controls, as was the case in ORX-KO mice. The difference in AP disappeared after treatment with an alpha-blocker but not with a beta-blocker, indicating lower sympathetic vasoconstrictor outflow. Stimulation of the perifornical area (PFA) in urethane-anesthetized ORX/ATX-Tg mice elicited smaller and shorter-lasting increases in AP, HR, and ventilation, and skeletal muscle vasodilation than in WT controls. In addition, air jet stress-induced elevations of AP and HR were attenuated in conscious ORX/ATX-Tg mice. After pretreatment with a beta-blocker, atenolol, stimulation of PFA suppressed phenylephrine (50 microg/kg iv)-induced bradycardia (DeltaHR=-360+/-29 beats/min without PFA stimulation vs. -166+/-26 during stimulation) in WT. This demonstrated the resetting of the baroreflex. In ORX/ATX-Tg mice, however, no significant suppression was observed (-355+/-16 without stimulation vs. -300+/-30 during stimulation). The present study provided further support for our hypothesis that orexin-containing neurons in PFA play a role as a master switch to activate multiple efferent pathways of the defense response and also operate as a regulator of basal AP.
authors.affiliation: Department of Molecular and Integrative Physiology, Chiba University Graduate School of Medicine, 1-8-1 Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
authors.forename: Yasuichiro
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kuwaki
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000067699:Ataxin-3; D001262:Atenolol / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy; D003243:Consciousness; D046690:Deep Brain Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000098:blood supply / Q000294:innervation / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics; D000068797:Orexins; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D000068797:Orexins; D014157:Transcription Factors; D010656:Phenylephrine; D001262:Atenolol; D000067699:Ataxin-3; C511594:Atxn3 protein, mouse; D011224:Prazosin