title: Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension.
abstract: The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague-Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10μg/h) or vehicle via osmotic minipump for 4weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91(phox)) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM.
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Hong-Bao
authors.initials: HB
authors.lastname: Li
authors.affiliation: Department of Physiology, Shantou University Medical College, Shantou 515041, China. Electronic address: dnqin@stu.edu.cn.
authors.forename: Da-Nian
authors.initials: DN
authors.lastname: Qin
authors.affiliation: Department of Public Health, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Le
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Yu-Wang
authors.initials: YW
authors.lastname: Miao
authors.affiliation: Department of Physiology, Dalian Medical University, Dalian 116044, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Sanaitang Hospital, Lanzhou 730030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Xin-Ai
authors.initials: XA
authors.lastname: Song
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhu
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China. Electronic address: ykang@mail.xjtu.edu.cn.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Kang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage; D062186:Arterial Pressure / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D007263:Infusions, Parenteral; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D017706:Lisinopril / Q000008:administration & dosage*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; D000975:Antioxidants; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D016753:Interleukin-10; D017706:Lisinopril; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D007703:Peptidyl-Dipeptidase A
keywords: Angiotensin-converting enzyme; Cytokines; Hypertension; Hypothalamic paraventricular nucleus; Oxidative stress; Rostral ventrolateral medulla