Orexin neuron-mediated skeletal muscle vasodilation and shift of baroreflex during defense response in mice.
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.
Zhang
Wei
W
Department of Molecular and Integrative Physiology, Chiba University Graduate School of Medicine, 1-8-1 Chuo-ku, Chiba 260-8670, Japan.
Sakurai
Takeshi
T
Fukuda
Yasuichiro
Y
Kuwaki
Tomoyuki
T
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*
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