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The Orexin System and Hypertension.

Michael J Huber1, Qing-Hui Chen1, Zhiying Shan2

  • 1Department of Kinesiology and Integrative Physiology, Michigan Technological University, SDC 231, 1400 Townsend Drive, Houghton, MI, 49931, USA.

Cellular and Molecular Neurobiology
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PubMed
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Orexin signaling hyperactivity contributes to hypertension. Blocking orexin receptors lowers blood pressure in hypertensive rat models, suggesting a therapeutic target for high blood pressure.

Keywords:
HypertensionOrexinSalt-sensitive hypertensionSympathetic nerve activity

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Area of Science:

  • Neuroscience
  • Cardiovascular Physiology
  • Pharmacology

Background:

  • Hypertension is a complex condition with significant cardiovascular implications.
  • The orexin system, known for regulating sleep-wake cycles, is increasingly implicated in cardiovascular control.
  • Understanding the orexin system's role in blood pressure regulation is crucial for developing novel antihypertensive strategies.

Purpose of the Study:

  • To review and synthesize evidence on the role of orexin signaling in blood pressure control.
  • To explore the potential link between orexin system hyperactivity and various models of hypertension.
  • To evaluate orexin receptor blockade as a potential therapeutic approach for hypertension.

Main Methods:

  • Review of experimental data from multiple animal models of hypertension, including spontaneously hypertensive rats (SHR), BPH/2J mice, Sprague-Dawley rats, and obese Zucker rats.
  • Analysis of studies investigating the effects of pharmacological orexin receptor blockade on blood pressure and sympathetic nerve activity (SNA).
  • Examination of the central orexin system's activity and orexin receptor 1's influence on neuronal firing and SNA in hypertensive models.

Main Results:

  • Pharmacological blockade of orexin receptors reduced blood pressure in spontaneously hypertensive rats (SHR) but not in normotensive Wistar-Kyoto rats.
  • Increased orexin system activity was associated with elevated blood pressure and sympathetic nerve activity (SNA) in genetic models of neurogenic hypertension (BPH/2J mice).
  • Stress-induced hypertension in Sprague-Dawley rats and obesity-related hypertension in obese Zucker rats were linked to an overactive central orexin system and orexin receptor 1 upregulation, respectively, augmenting SNA and contributing to elevated blood pressure.

Conclusions:

  • Hyperactivity of the orexin system is strongly implicated in the pathogenesis of hypertension across various experimental models.
  • The orexin system's contribution to elevated sympathetic nerve activity (SNA) is a key mechanism linking orexin signaling to increased blood pressure.
  • Targeting the orexin system, particularly through orexin receptor blockade, represents a promising therapeutic avenue for managing hypertension, including potentially salt-sensitive forms.