**Conflict of interest**

hypocretin have been consistently observed [63, 72]. Patients with the lowest levels tend to have a more severe and rapid disease course, running with tetraplegia and respiratory failure. The mechanism underlying the lack or very decreased levels of hypocretin in Guillain-Barré syndrome remains unknown, but an immune-mediated hypothalamic dysfunction has been hypothesized.

Almost all bodily functions are dependent on the autonomic nervous system (ANS), which exerts precise control over visceral functions. Sleep disruption causes an increased activity of the sympathetic nervous system in association with an elevated blood pressure, and the risks of hypertension and cardiovascular disease are increased as a consequence of either strong acute or long-term sleep disruption [73]. The hypocretin/orexin system also contributes to the regulation of cardiovascular functions via the autonomic nervous system. Hypocretin/ orexin neurons project to several brain regions involved in the regulation of cardiovascular activity, namely the paraventricular nucleus (PVN), nucleus tractus solitarius, and the rostral

Over-activation of the hypocretin/orexin system has been implicated in the pathogenesis of hypertension. It has been shown that the central administration of orexins A and B increases arterial blood pressure and elicits tachycardia in animal models [74]. Conversely, orexin/ ataxin-3 transgenic rats, lacking orexin neurons, have a significantly reduced sympathetic nervous system tone and a lower systolic blood pressure when compared with controls [75]. In addition, spontaneously hypertensive rats (SHRs) have increased levels of hypocretin/ orexin [74] that, when blocked by the oral administration of almorexant or by intracerebroventricular injections of TCSOX229, led to a significant reduction of systolic blood pressure while not affecting arterial blood pressure in normotensive animals [76, 77]. These data suggest that hypocretin/orexin may play a significant role in the pathogenesis of hypertension. In humans, Dauvilliers and coworkers reported a lower cardiac activation associated with periodic leg movements during sleep in narcoleptic patients which was proposed to be related to changes in baroreflex sensitivity [78]. The same group found a large percentage of diastolic non-dippers, with 64% failing to achieve the 15% fall point on diastolic blood pressure [79], and recent data suggested that narcoleptic patients displayed a nighttime non-dipping blood pressure pattern with increased systolic blood pressure during nighttime REM sleep [80].

The blunted cardiac activation and sleep-related blood pressure fall in narcoleptic patients may be clinically relevant and may indicate an increased risk for cardiovascular events among

In summary, despite being present throughout the animal kingdom, the precise sleep function is still relatively elusive. However, it is evident that sleep regulation is fundamental for survival having the hypothalamus a significant role in those modulatory processes through the orexin/hypocretin and the MCH neurons. Nevertheless, further studies on sleep physiology

attributable to a potentially clinically significant hypocretin/orexin deficiency.

**5. Conclusion**

**4.4. Orexin and sleep-related physical disorders: cardiovascular disease**

38 Hypothalamus in Health and Diseases

ventrolateral medulla (RVLM), all areas of the central autonomic network [74].

The authors declare no conflict of interest.
