Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

Journal Article · Fri May 01 04:00:00 EDT 2015 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2015.02.023· OSTI ID:22465748

Yu, Xiao-Jing ^[1]; Zhang, Dong-Mei ^[2]; Jia, Lin-Lin; Qi, Jie; Song, Xin-Ai; Tan, Hong ^[1]; Cui, Wei ^[3]; Chen, Wensheng ^[4]; Zhu, Guo-Qing ^[5]; Qin, Da-Nian ^[6]; Kang, Yu-Ming ^[1]

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1. 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)
2. Department of Physiology, Dalian Medical University, Dalian 116044 (China)
3. Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University Health Science Center, Xi'an 710061 (China)
4. Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032 (China)
5. Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China)
6. Department of Physiology, Shantou University Medical College, Shantou 515041 (China)

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. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines. • PVN inhibition of NF-κB attenuates PVN NF-κB p65 activity and oxidative stress.

• OSTI ID: 22465748
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 284; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
EXCITATION
HEART
HYPERTENSION
HYPERTROPHY
INFLAMMATION
INFUSION
INHIBITION
LYMPHOKINES
MESSENGER-RNA
MONOCYTES
MYOSIN
NAD
OXIDASES
OXIDATION
PEPTIDES
RATS
STRESSES
TIBIA
WEIGHT