title: Oxidative stress in the cardiovascular center has a pivotal role in the sympathetic activation in hypertension.
abstract: Activation of the sympathetic nervous system has an important role in the pathogenesis of hypertension. However, the precise mechanisms involved are not fully understood. Oxidative stress may be important in hypertension as well as in other cardiovascular disorders. We investigated the role of oxidative stress, particularly in the rostral ventrolateral medulla (RVLM), which is known as the cardiovascular center in the brainstem, in the activation of the sympathetic nervous system in hypertension. We observed that the reactive oxygen species (ROS) production increases in the RVLM in hypertensive rats, thereby enhancing the central sympathetic outflow, which leads to hypertension. Furthermore, the environmental factors of high salt intake and a high-calorie diet may also increase the ROS production in the RVLM, thereby activating the central sympathetic outflow and increasing the risk of hypertension. The activation of the nicotinamide adenine dinucleotide phosphate oxidase via the angiotensin type 1 (AT1) receptors is suggested to be the major source of ROS production, and an altered downstream signaling pathway is involved in the activation of the RVLM neurons, leading to enhanced central sympathetic outflow and hypertension. Thus, the brain AT1 receptors may be novel therapeutic targets, and, in fact, oral treatment with angiotensin receptor blockers has been found to inhibit the central AT1 receptors, despite the blood-brain barrier.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. hyoshi@cardiol.med.kyushu-u.ac.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
mesh_terms: D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D004195:Disease Models, Animal; D006973:Hypertension / Q000503:physiopathology*; D020646:Intralaminar Thalamic Nuclei / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1