Orexins and the cardiovascular events of awakening

Abstract

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.

Dynamic coupling between the central and autonomic nervous systems during sleep: A review

“…The brain is connected to cardiac myocytes and arteriolar smooth muscle cells, which are the CV autonomic effectors, by di-synaptic pathways involving preganglionic and ganglionic autonomic neurons (Silvani et al, 2016). In the afferent direction, changes in blood vessel stretch and skin temperature, which are affected by skin vessel tone, are detected by baroreceptors and thermoreceptors and fed back to the brain (Silvani, 2017; Silvani et al, 2015). Changes in breathing such as those seen when transitioning from wakefulness to sleep (Trinder and Nicholas, 2000), also modulate the ANS both directly, through CNS circuits, and reflexively, for example by changing lung stretch as a function of sleep-related reduction in tidal volume (Colrain et al, 1987).…”

“…The lower values of SNA to the skin during NREM sleep compared to wakefulness (Takeuchi et al, 1994) may result from inhibition of a thermoregulatory pathway for heat generation and retention, which includes the preoptic hypothalamus and the medullary raphe (Morrison, 2016). On the other hand, the occurrence of lower values of SNA to the skeletal muscles (Somers et al, 1993) and kidneys (Miki et al, 2003) during NREM sleep may result from (Silvani, 2017; Silvani and Dampney, 2013): a) inhibition of the hypothalamic paraventricular nucleus (Uschakov et al, 2006), a master ANS controller that integrates neuroendocrine, homeostatic and stress responses during wakefulness (Thompson and Swanson, 2003); b) inhibition of the pedunculopontine nucleus between the caudal midbrain and rostral pons (el Mansari et al, 1989), a region potentially contributing to central autonomic commands associated with locomotion during wakefulness (Garcia-Rill et al, 1987; Padley et al, 2007); and c) potentiation of the baroreceptor reflex, through a pathway that involves the pontine parabrachial nucleus (Saito et al, 1977) and the medullary nucleus of the solitary tract (Eguchi and Satoh, 1980). In particular, increases in parabrachial nucleus activity may inhibit the baroreflex at the level of the first afferent relay, which is the nucleus of the solitary tract (Felder and Mifflin, 1988).…”

Orexin A Suppresses Oxidized LDL Induced Endothelial Cell Inflammation via MAPK p38 and NF‐κB Signaling Pathway

“…The hypothalamic orexin A is a small neuropeptide, and this peptide influences diverse physiological processes such as control of food intake , sleep–wake behavior , arousal, and energy balance . Orexin A activates the cellular signals mainly by binding to the orexin‐1 receptor (OX1R), an important G‐protein coupled receptor .…”