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1 Department of Molecular & Integrative Physiology, Chiba University Graduate School of Medicine, Chiba, Chiba 260-8670, Japan
2 Department of Molecular Pharmacology, Graduation School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Exploratory Research for Advance Technology Yanagisawa Orphan Project, Japan Science and Technology Corporation, Tokyo, Tokyo 135-0064, Japan
3 Department of Autonomic Physiology, Chiba University Graduate School of Medicine, Chiba, Chiba 260-8670, Japan
4 Department of Molecular & Integrative Physiology, Chiba University Graduate School of Medicine, Chiba, Chiba 260-8670, Japan; Department of Autonomic Physiology, Chiba University Graduate School of Medicine, Chiba, Chiba 260-8670, Japan
* To whom correspondence should be addressed. E-mail: kuwaki{at}faculty.chiba-u.jp.
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 mice (ORX-KO). Here we examined whether the same was true in orexin neuron-ablated mice (ORX/ATX-Tg). In addition, we examined the other features of the defense response; skeletal muscular vasodilation and shift of baroreceptor reflex. Both in anesthetized and conscious conditions, basal AP in ORX/ATX-Tg was significantly lower by ~20 mmHg than that in WT, as was the case in ORX-KO. The difference in AP disappeared after treatment with an 
-blocker but not with a 
-blocker, indicating lower sympathetic vasoconstrictor outflow. Stimulation of the perifornical area (PFA) in urethane-anesthetized ORX/ATX-Tg elicited smaller and shorter-lasting increases in AP, HR, and ventilation, and skeletal muscle vasodilation than that in the wild-type controls (WT). In addition, air jet stress-induced elevations of AP and HR were attenuated in conscious ORX/ATX-Tg. After pretreatment with a -blocker, atenolol, stimulation of PFA suppressed phenylephrine (50 µg/kg, iv)-induced bradycardia (
HR = -360±29 bpm without PFA stimulation vs. -166±26 during stimulation) in WT. This demonstrated the resetting of the baroreflex. In ORX/ATX-Tg, 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.
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