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Activated microglia in the hypothalamic paraventricular nucleus contribute to sympathoexcitation in heart failure
Author(s) -
Kang YuMing,
Su YuKun,
Ma Ying,
Qin DaNian,
Guo Zheng,
Lei JingHui,
Guo ZhouWei,
Zheng JinPing,
Francis Joseph
Publication year - 2009
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.23.1_supplement.792.8
Subject(s) - pyrrolidine dithiocarbamate , microglia , medicine , proinflammatory cytokine , endocrinology , heart failure , hypothalamus , ventricle , inflammation , nf κb
Recent studies have demonstrated that the elevation of proinflammatory cytokines (PIC) in the paraventricular nucleus of the hypothalamus (PVN) contributes to sympathoexcitation in heart failure (HF). However, the origin of these cytokines is unknown. We hypothesized that microglia are activated in the PVN, and that contribute significantly to release the PIC that stimulate sympathoexcitatory systems in HF. Adult male Sprage‐Dawley rats underwent left anterior descending coronary artery ligation to induce HF or sham surgery (SHAM). Subsequently, animals received bilateral PVN infusion of the nuclear factor κB (NF‐κB) inhibitor pyrrolidine dithiocarbamate (PDTC, 5µg/hr), or vehicle for 4 weeks. Compared with SHAM rats, HF rats had higher levels of TNF‐α and more activated microglia in the PVN, higher TNF‐α protein expression in myocardium cells, and augmented renal sympathetic nerve activity. HF rats also had higher left ventricular end‐diastolic pressure (LVEDP), and higher right ventricle/body weight (BW) and lung/BW ratio. PDTC ameliorated cardiac dysfunction in HF rats, decreased TNF‐α in the PVN and cardiac tissues, reduced the numbers of activated microglia, and downregulated renal sympathetic drive. These findings suggest that activated microglia in the PVN contribute to the sympathoexcitation by releasing cytokines in HF. Supported by NIH HL‐080544.