Role of Orexin-A in Hypertension and Obesity

  • Roberta Imperatore
  • Letizia Palomba
  • Luigia Cristino
Hypertension and Metabolic Syndrome (J Sperati, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Hypertension and Metabolic Syndrome


Purpose of Review

Hypertension is one of the most challenging health problems inducing cerebrovascular disease and high percentage of death when associated with diabetes, dyslipidemias, and obesity. Orexin/hypocretin is a peptide expressed by a small number of neurons of the dorsolateral hypothalamus, a brain feeding and autonomic “fight-or-flight” regulatory center. According to this function, orexin has been demonstrated to evoke cardiovascular responses, heart rate, hypertension, hyperarousal, hyperphagia, and obesity. The focus of this review is to provide an overview about the mechanism through which orexin regulates food intake and cardiovascular responses and its role in the pathogenesis of obesity and hypertension which could be of great interest to establish possible new therapies.

Recent Findings

In normal rats and mice, central administration of orexin increases food intake, blood pressure, and sympathetic nerve activity and these effects are blocked by selective orexin receptor antagonist SB-334867 or almorexant. Moreover, upregulation of orexin signaling, in combination with elevation of epinephrine and norepinephrine circulating levels, occurs in rats exposed to chronic stress, in models of spontaneous hypertension (SHR and BPH/2J Schlager mice) and in obese mice (ob/ob or mice fed with high fat diet). Therefore, hyperactivity of orexinergic neurons could be a factor in the development of obesity and essential hypertension.


Because of their widespread projections to the brain regions involved in appetite and cardiovascular responses, as far down as sympathetic preganglionic neurons in the spinal cord, orexin evokes sympathetically mediated cardiovascular responses. Lasting upregulation of orexin signaling can lead to hyperphagia, obesity, and hypertensive state. Dual orexin receptor antagonists (DORAs) and selective orexin receptor antagonists (SORAs) have antihypertensive effects that could be of clinical use for regulation of food intake and hypertension, supporting the role of orexinergic neurons as critical checkpoint in the neurogenic control of metabolic and cardiovascular functions.


Orexin Obesity Hypertension Catecholamine Epinephrine Norepinephrine 





Angiotensin-converting enzyme


Adreno corticotropic hormone


Nucleus ambiguous


Angiotensin II


Arcuate nucleus


Angiotensin type 1 receptor




High blood pressure mouse


Normotensive blood pressure mouse


Corticotropin-releasing factor


Adrenocorticotropin-releasing hormone


Dorsomedial nucleus




Green fluorescent protein


Hypocretin 1


Hypocretin 2


High-fat diet


Hypothalamic-pituitary-adrenal axis


Heart rate




Intermediolateral column






Locus coeruleus


Lateral hypothalamic area


Lean Zucker rats


Mean arterial pressure


Melanocyte Stimulating Hormone






Nucleus tractus solitaries


Orexin-1 receptor


Orexin-2 receptor


Ox1R and Ox2R






OX-A and OX-B


Obese Zucker rats


Periaqueductal gray




Paraventricular nucleus


Renin-angiotensin system


Response sympathetic nervous autonomous


Rostral ventrolateral medulla


Rostral ventromedial medulla




Supra-chiasmatic nucleus


Standard-fat diet


Spontaneously hypertensive rat


Stress-induced hypertensive rats


Sympathetic nerve activity


Sympathetic preganglionic neurons


Paraventricular nucleus


Zona fasciculate


Zona reticularis


Wistar Kyoto rats


Compliance with Ethical Standards

Conflict of Interest

Drs. Imperatore, Palomba and Cristino declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Roberta Imperatore
    • 1
    • 2
  • Letizia Palomba
    • 3
  • Luigia Cristino
    • 1
  1. 1.Endocannabinoid Research Group, Institute of Biomolecular ChemistryCNRPozzuoliItaly
  2. 2.Department of Science and TechnologyUniversity of SannioBeneventoItaly
  3. 3.Department of Biomolecular ScienceUniversity of Urbino “Carlo Bo”UrbinoItaly

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