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Targeting Interleukin-1 beta to Suppress Sympathoexcitation in Hypothalamic Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats.
Cardiovasc Toxicol 2016; 16(3):298-306CT

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+Show Affiliations

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 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 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 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 Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.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.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 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 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 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 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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26304161

Citation

Qi, Jie, et al. "Targeting Interleukin-1 Beta to Suppress Sympathoexcitation in Hypothalamic Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats." Cardiovascular Toxicology, vol. 16, no. 3, 2016, pp. 298-306.
Qi J, Zhao XF, Yu XJ, et al. Targeting Interleukin-1 beta to Suppress Sympathoexcitation in Hypothalamic Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats. Cardiovasc Toxicol. 2016;16(3):298-306.
Qi, J., Zhao, X. F., Yu, X. J., Yi, Q. Y., Shi, X. L., Tan, H., ... Kang, Y. M. (2016). Targeting Interleukin-1 beta to Suppress Sympathoexcitation in Hypothalamic Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats. Cardiovascular Toxicology, 16(3), pp. 298-306. doi:10.1007/s12012-015-9338-7.
Qi J, et al. Targeting Interleukin-1 Beta to Suppress Sympathoexcitation in Hypothalamic Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats. Cardiovasc Toxicol. 2016;16(3):298-306. PubMed PMID: 26304161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting Interleukin-1 beta to Suppress Sympathoexcitation in Hypothalamic Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats. AU - Qi,Jie, AU - Zhao,Xiu-Fang, AU - Yu,Xiao-Jing, AU - Yi,Qiu-Yue, AU - Shi,Xiao-Lian, AU - Tan,Hong, AU - Fan,Xiao-Yan, AU - Gao,Hong-Li, AU - Yue,Li-Ying, AU - Feng,Zhi-Peng, AU - Kang,Yu-Ming, PY - 2015/8/26/entrez PY - 2015/8/26/pubmed PY - 2017/2/14/medline KW - Hypothalamic paraventricular nucleus KW - Interleukin-1 beta KW - NLRP3 KW - Oxidative stress KW - Salt-sensitive hypertension SP - 298 EP - 306 JF - Cardiovascular toxicology JO - Cardiovasc. Toxicol. VL - 16 IS - 3 N2 - 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. SN - 1559-0259 UR - https://www.unboundmedicine.com/medline/citation/26304161/Targeting_Interleukin_1_beta_to_Suppress_Sympathoexcitation_in_Hypothalamic_Paraventricular_Nucleus_in_Dahl_Salt_Sensitive_Hypertensive_Rats_ L2 - https://dx.doi.org/10.1007/s12012-015-9338-7 DB - PRIME DP - Unbound Medicine ER -