title: Targeting Interleukin-1 beta to Suppress Sympathoexcitation in Hypothalamic Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats.
abstract: Findings from our laboratory indicate that expressions of some proinflammatory cytokines such as tumor necrosis factor, interleukin-6 and oxidative stress responses are increased in the hypothalamic paraventricular nucleus (PVN) and contribute to the progression of salt-sensitive hypertension. In this study, we determined whether interleukin-1 beta (IL-1β) activation within the PVN contributes to sympathoexcitation during development of salt-dependent hypertension. Eight-week-old male Dahl salt-sensitive (S) rats received a high-salt diet (HS, 8 % NaCl) or a normal-salt diet (NS, 0.3 % NaCl) for 6 weeks, and all rats were treated with bilateral PVN injection of gevokizumab (IL-1β inhibitor, 1 μL of 10 μg) or vehicle once a week. The mean arterial pressure (MAP), heart rate (HR) and plasma norepinephrine (NE) were significantly increased in high-salt-fed rats. In addition, rats with high-salt diet had higher levels of NOX-2, NOX-4 [subunits of NAD (P) H oxidase], IL-1β, NLRP3 (NOD-like receptor family pyrin domain containing 3), Fra-LI (an indicator of chronic neuronal activation) and lower levels of IL-10 in the PVN than normal-diet rats. Bilateral PVN injection of gevokizumab decreased MAP, HR and NE, attenuated the levels of oxidative stress and restored the balance of cytokines. These findings suggest that IL-1β activation in the PVN plays a role in salt-sensitive hypertension.
authors: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors: Jie
authors: J
authors: Qi
authors: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors: Xiu-Fang
authors: XF
authors: Zhao
authors: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors: Xiao-Jing
authors: XJ
authors: Yu
authors: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors: Qiu-Yue
authors: QY
authors: Yi
authors: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
authors: Xiao-Lian
authors: XL
authors: Shi
authors: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.|Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
authors: Hong
authors: H
authors: Tan
authors: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors: Xiao-Yan
authors: XY
authors: Fan
authors: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors: Hong-Li
authors: HL
authors: Gao
authors: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors: Li-Ying
authors: LY
authors: Yue
authors: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors: Zhi-Peng
authors: ZP
authors: Feng
authors: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China. ykang@mail.xjtu.edu.cn.
authors: Yu-Ming
authors: YM
authors: Kang
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary; D013481:Superoxides / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000959:Antihypertensive Agents; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D017673:Sodium Chloride, Dietary; D013481:Superoxides; D016753:Interleukin-10; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C547697:gevokizumab; D009638:Norepinephrine
keywords: Hypothalamic paraventricular nucleus; Interleukin-1 beta; NLRP3; Oxidative stress; Salt-sensitive hypertension