The hypothalamic peptide orexin plays a role in many physiological systems including feeding behavior, sleep-wakefulness, reward system, stress, and nociception. In addition, it is now clear that orexin is involved in the central regulation of cardiorespiratory function. Here, we review the cardiorespiratory effects elicited by central orexin and consider the physiological role of this peptide in central cardiorespiratory control in normal and pathophysiological states. Orexin neurons are found exclusively in the hypothalamus but project to almost all brain regions including cardiorespiratory regulatory areas, where their receptors are also expressed. Administration of orexin into the nucleus tractus solitarius, rostral ventrolateral medulla, rostral ventromedial medulla, and spinal cord increases blood pressure, heart rate, and sympathetic nerve activity. Orexin neurons stimulate respiration and are sensitive to changes in pH. Orexin knockout mice have apnoeic episodes in sleep. Therefore, orexin may be a potentially important therapeutic target for the treatment of cardiorespiratory disorders.
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