Orexin and Central Modulation of Cardiovascular and Respiratory Function

Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 33)


Orexin makes an important contribution to the regulation of cardiorespiratory function. When injected centrally under anesthesia, orexin increases blood pressure, heart rate, sympathetic nerve activity, and the amplitude and frequency of respiration. This is consistent with the location of orexin neurons in the hypothalamus and the distribution of orexin terminals at all levels of the central autonomic and respiratory network. These cardiorespiratory responses are components of arousal and are necessary to allow the expression of motivated behaviors. Thus, orexin contributes to the cardiorespiratory response to acute stressors, especially those of a psychogenic nature. Consequently, upregulation of orexin signaling, whether it is spontaneous or environmentally induced, can increase blood pressure and lead to hypertension, as is the case for the spontaneously hypertensive rat and the hypertensive BPH/2J Schlager mouse. Blockade of orexin receptors will reduce blood pressure in these animals, which could be a new pharmacological approach for the treatment of some forms of hypertension. Orexin can also magnify the respiratory reflex to hypercapnia in order to maintain respiratory homeostasis, and this may be in part why it is upregulated during obstructive sleep apnea. In this pathological condition, blockade of orexin receptors would make the apnea worse. To summarize, orexin is an important modulator of cardiorespiratory function. Acting on orexin signaling may help in the treatment of some cardiovascular and respiratory disorders.


Blood pressure Chemoreflex Heart rate Hypercapnia Hypocretin Obstructive sleep apnea Ox1R Ox2R Psychological stress Respiration Rostral ventrolateral medulla Schlager mouse SHR Sympathetic 



Supported by grants from the National Health of Medical Research Council of Australia and from the Ministry of Education, Science, Culture, and Sports in Japan.

Conflict of Interest

The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


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Authors and Affiliations

  1. 1.School of Medical SciencesUniversity of New South WalesSydneyAustralia
  2. 2.Department of Physiology, Graduate School of Medical & Dental SciencesKagoshima UniversityKagoshimaJapan

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