Orexins and the cardiovascular events of awakening.

This brief review aims to provide an updated account of the cardiovascular events of awakening, proposing a testable conceptual framework that links these events with the neural control of sleep and the autonomic nervous system, with focus on the hypothalamic orexin (hypocretin) neurons. Awakening from non-rapid-eye-movement sleep entails coordinated changes in brain and cardiovascular activity: the neural "flip-flop" switch that governs state transitions becomes biased toward the ascending arousal systems, arterial blood pressure and heart rate rise toward waking values, and distal skin temperature falls. Arterial blood pressure and skin temperature are sensed by baroreceptors and thermoreceptors and may positively feedback on the brain wake-sleep switch, thus contributing to sharpen, coordinate, and stabilize awakening. These effects may be enhanced by the hypothalamic orexin neurons, which may modulate the changes in blood pressure, heart rate, and skin temperature upon awakening, while biasing the wake-sleep switch toward wakefulness through direct neural projections. A deeper understanding of the cardiovascular events of awakening and of their links with skin temperature and the wake-sleep neural switch may lead to better treatments options for patients with narcolepsy type 1, who lack the orexin neurons.