Premium
Contribution of brain nuclear factor‐kappa B to the pathogenesis of heart failure
Author(s) -
Ma Ying,
Kang YuMing,
Yang ZhiMing,
Zheng JinPing,
Francis Joseph
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.952.19
Subject(s) - endocrinology , angiotensin ii , medicine , proinflammatory cytokine , hypothalamus , oxidative stress , angiotensin ii receptor type 1 , inflammation , norepinephrine , heart failure , sympathetic nervous system , chemistry , receptor , blood pressure , dopamine
Previous studies have shown nuclear factor kappa B (NF‐κB) is a major mediator facilitating the synthesis of proinflammatory cytokines (PIC) both in the peripheral and central nervous system. In this study we determined, whether blockade of brain NF‐κB attenuates PIC and oxidative stress in heart failure (HF) rats. Adult male Sprague‐Dawley rats were implanted with intracerebroventricular (ICV) cannulae and subjected to coronary artery ligation to induce HF or sham surgery (SHAM). Subsequently, animals were ICV treated with SN50 (2μg/hr), a membrane permeable peptide which inhibits nuclear translocation of NF‐κB, or vehicle (VEH) for 4 weeks. HF‐induced increases in the expression of NF‐κB, AT1‐R and NADPH oxidase gene in paraventricular nucleus (PVN) of hypothalamus, and TNF‐α, IL‐1β, IL‐6 and angiotensin type 1 receptor (AT1‐R) in hypothalamus compared with sham rats. The HF rats also had increased plasma norepinephrine (NE), an indirect indicator of sympathetic activity. In contrast, ICV treatment with SN50 attenuated the expression of PIC, NF‐κB, AT1‐R and oxidative stress gene in the PVN compared with VEH‐treated HF rats. Treatment with SN50 also reduced plasma levels of NE, angiotensin II (ANG II) and PIC, and lung weight to body weight ratio. These findings suggest NF‐κB may be one key mediator stimulating the synthesis of brain RAS and PIC in HF.