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Published on: February 14, 2021
Orexin neuron-mediated skeletal muscle vasodilation and shift of baroreflex during defense response in mice
Wei Zhang1, Takeshi Sakurai, Yasuichiro Fukuda
1Department of Molecular and Integrative Physiology, Chiba University Graduate School of Medicine, 1-8-1 Chuo-ku, Chiba 260-8670, Japan.
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.
Insights
Orexin neurons regulate the body's defense response. Ablating these neurons in mice reduced arterial pressure and blunted key defense reactions, indicating orexin's role in activating these pathways.
Area of Science:
- Neuroscience
- Physiology
Background:
- Orexin-containing neurons are crucial for regulating arousal and energy balance.
- Previous studies showed attenuated defense responses in prepro-orexin knockout mice.
Purpose of the Study:
- To investigate the role of orexin neurons in the defense response using orexin neuron-ablated mice (ORX/ATX-Tg).
- To examine effects on arterial pressure, heart rate, ventilation, skeletal muscle vasodilation, and baroreceptor reflex.
Main Methods:
- Comparison of basal physiological parameters in ORX/ATX-Tg and wild-type (WT) mice under anesthetized and conscious conditions.
- Assessment of defense response activation via perifornical area (PFA) stimulation and air jet stress.
- Pharmacological blockade of sympathetic and parasympathetic systems to analyze baroreflex function.
Main Results:
- ORX/ATX-Tg mice exhibited significantly lower basal arterial pressure and attenuated increases in arterial pressure, heart rate, and ventilation upon PFA stimulation.
- Skeletal muscle vasodilation and air jet stress responses were also blunted in ORX/ATX-Tg mice.
- The baroreceptor reflex resetting, observed in WT mice, was absent in ORX/ATX-Tg mice.
Conclusions:
- Orexin neurons in the PFA act as a master switch for activating multiple defense response pathways.
- These neurons are critical regulators of basal arterial pressure and cardiovascular responses during stress.
