title: The Orexin System and Hypertension.
abstract: In this review, we focus on the role of orexin signaling in blood pressure control and its potential link to hypertension by summarizing evidence from several experimental animal models of hypertension. Studies using the spontaneously hypertensive rat (SHR) animal model of human essential hypertension show that pharmacological blockade of orexin receptors reduces blood pressure in SHRs but not in Wistar-Kyoto rats. In addition, increased activity of the orexin system contributes to elevated blood pressure and sympathetic nerve activity (SNA) in dark-active period Schlager hypertensive (BPH/2J) mice, another genetic model of neurogenic hypertension. Similar to these two models, Sprague-Dawley rats with stress-induced hypertension display an overactive central orexin system. Furthermore, upregulation of the orexin receptor 1 increases firing of hypothalamic paraventricular nucleus neurons, augments SNA, and contributes to hypertension in the obese Zucker rat, an animal model of obesity-related hypertension. Finally, we propose a hypothesis for the implication of the orexin system in salt-sensitive hypertension. All of this evidence, coupled with the important role of elevated SNA in increasing blood pressure, strongly suggests that hyperactivity of the orexin system contributes to hypertension.
authors.affiliation: Department of Kinesiology and Integrative Physiology, Michigan Technological University, SDC 231, 1400 Townsend Drive, Houghton, MI, 49931, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Huber
authors.affiliation: Department of Kinesiology and Integrative Physiology, Michigan Technological University, SDC 231, 1400 Townsend Drive, Houghton, MI, 49931, USA.
authors.forename: Qing-Hui
authors.initials: QH
authors.lastname: Chen
authors.affiliation: Department of Kinesiology and Integrative Physiology, Michigan Technological University, SDC 231, 1400 Townsend Drive, Houghton, MI, 49931, USA. zhiyings@mtu.edu.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Shan
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D064446:Orexin Receptors / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011924:Rats, Zucker
chemical_list: D064446:Orexin Receptors; D000068797:Orexins
keywords: Hypertension; Orexin; Salt-sensitive hypertension; Sympathetic nerve activity