Tags

Type your tag names separated by a space and hit enter

Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress.
Toxicol Appl Pharmacol 2015; 284(3):315-22TA

Abstract

We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar-Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy.

Authors+Show Affiliations

Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.Department of Physiology, Dalian Medical University, Dalian 116044, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China.Department of Physiology, Shantou University Medical College, Shantou 515041, China. Electronic address: dnqin@stu.edu.cn.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. Electronic address: ykang@mail.xjtu.edu.cn.

Pub Type(s)

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

Language

eng

PubMed ID

25759242

Citation

Yu, Xiao-Jing, et al. "Inhibition of NF-κB Activity in the Hypothalamic Paraventricular Nucleus Attenuates Hypertension and Cardiac Hypertrophy By Modulating Cytokines and Attenuating Oxidative Stress." Toxicology and Applied Pharmacology, vol. 284, no. 3, 2015, pp. 315-22.
Yu XJ, Zhang DM, Jia LL, et al. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress. Toxicol Appl Pharmacol. 2015;284(3):315-22.
Yu, X. J., Zhang, D. M., Jia, L. L., Qi, J., Song, X. A., Tan, H., ... Kang, Y. M. (2015). Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress. Toxicology and Applied Pharmacology, 284(3), pp. 315-22. doi:10.1016/j.taap.2015.02.023.
Yu XJ, et al. Inhibition of NF-κB Activity in the Hypothalamic Paraventricular Nucleus Attenuates Hypertension and Cardiac Hypertrophy By Modulating Cytokines and Attenuating Oxidative Stress. Toxicol Appl Pharmacol. 2015 May 1;284(3):315-22. PubMed PMID: 25759242.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress. AU - Yu,Xiao-Jing, AU - Zhang,Dong-Mei, AU - Jia,Lin-Lin, AU - Qi,Jie, AU - Song,Xin-Ai, AU - Tan,Hong, AU - Cui,Wei, AU - Chen,Wensheng, AU - Zhu,Guo-Qing, AU - Qin,Da-Nian, AU - Kang,Yu-Ming, Y1 - 2015/03/07/ PY - 2014/11/18/received PY - 2015/02/18/revised PY - 2015/02/25/accepted PY - 2015/3/12/entrez PY - 2015/3/12/pubmed PY - 2015/6/30/medline KW - Cardiac hypertrophy KW - Hypertension KW - Hypothalamic paraventricular nucleus KW - NF-κB KW - Neurohormonal excitation SP - 315 EP - 22 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 284 IS - 3 N2 - We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar-Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/25759242/Inhibition_of_NF_κB_activity_in_the_hypothalamic_paraventricular_nucleus_attenuates_hypertension_and_cardiac_hypertrophy_by_modulating_cytokines_and_attenuating_oxidative_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(15)00080-0 DB - PRIME DP - Unbound Medicine ER -