Orexin neuron-mediated skeletal muscle vasodilation and shift of baroreflex during defense response in mice

Abstract

Zhang, Wei, Takeshi Sakurai, Yasuichiro Fukuda, and Tomoyuki Kuwaki. Orexin neuron-mediated skeletal muscle vasodilation and shift of baroreflex during defense response in mice. Am J Physiol Regul Integr Comp Physiol 290: R1654 -R1663, 2006. First published January 12, 2006 doi:10.1152/ajpregu.00704.2005We 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 ϳ20 mmHg than in wild-type (WT) controls, as was the case in ORX-KO mice. 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 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 ␤-blocker, atenolol, stimulation of PFA suppressed phenylephrine (50 g/kg iv)-induced bradycardia (⌬HR ϭ Ϫ360 Ϯ 29 beats/ min without PFA stimulation vs. Ϫ166 Ϯ 26 during stimulation) in WT. This demonstrated the resetting of the baroreflex. In ORX/ ATX-Tg mice, however, no significant suppression was observed (Ϫ355 Ϯ 16 without stimulation vs. Ϫ300 Ϯ 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.hypothalamus; stress; blood pressure; respiration OREXIN A AND B, also known as hypocretin 1 and 2, respectively, are hypothalamic neuropeptides. They are cleaved from a common precursor molecule, prepro-orexin, undergoing proteolytic processing (33,41). Although the localization of orexin-containing cell bodies is restricted to the hypothalamus, the orexin-containing fibers and terminals are widely distributed in the hypothalamus, thalamus, cerebral cortex, circumventricular organs, brain stem, and spinal cord (13,28). This anatomic feature establishes the basis that orexin contributes to multiple physiological functions, including feeding behavior, energy homeostasis, sleep-wake cycle, and regulation of the autonomic and neuroendocrine systems (25,36,41).At present, there are two genetically engineered mice models of orexin deficiency to study possible roles of intrinsic orexin in physiological functions mentioned above. One is the prepro-orexin knockout (ORX-KO) mouse that was developed by a conv...

Dopaminergic and non-dopaminergic value systems in conditioning and outcome-specific revaluation

“…This second mechanism of FSS can explain the observation that the kind of FSS that is assessed by actual consumption rather than by CS preference remains intact even after ORB and AMYG lesions (Hatfield et al, 1996;Dunn and Everitt, 1988 (Brown et al, 2004;Equation (9) (Braesicke, et al 2005). This influence is relayed from the hypothalamus to cardiovascular regulatory neurons in the medulla (Smith et al, 1990;Nakamura et al, 1992;Zhang et al, 2005Zhang et al, , 2006. The component of the blood pressure variable attributable to appetitive or aversive stimuli, B, is calculated as follows: A.6.2 Saccadic Output.…”

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“…This second mechanism of FSS can explain the observation that the kind of FSS that is assessed by actual consumption rather than by CS preference remains intact even after ORB l and AMYG lesions (Hatfield et al, 1996;Dunn and Everitt, 1988 (Braesicke, et al 2005). This influence is relayed from the hypothalamus to cardiovascular regulatory neurons in the medulla (Smith et al, 1990;Nakamura et al, 1992;Zhang et al, 2005Zhang et al, , 2006. The component of the blood pressure variable attributable to appetitive or aversive stimuli, B, is calculated as follows: …”

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“…42 This was because ABP was significantly lower in these hybrid ORX-ATX3 mice than in hybrid wild-type mice during wakefulness, but not during NREM sleep. 42 Other experiments, performed without taking sleep into account on ORX-KO 43 and ORX-ATX3 44 mice with mixed genetic background, reported lower values of ABP during behaviorallydetermined wakefulness in these mice compared with wild-type mice. Experiments on ORX-ATX3 rats found lower values of ABP compared with wild-type rats, with similar increases in ABP and HR upon awakening from NREM sleep.…”