Journal
BASIC RESEARCH IN CARDIOLOGY
Volume 106, Issue 3, Pages 473-483Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00395-011-0155-2
Keywords
Corticotrophin releasing hormone; Neurotransmitters; Hypothalamic paraventricular nucleus; Sympathetic nervous system; Heart failure
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Funding
- National Natural Science Foundation of China [81070199]
- US National Institutes of Health (NIH) [RO1-HL-080544-01]
- Fundamental Research Funds for the Central Universities of China [08142001]
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Recent studies indicate that systemic administration of tumor necrosis factor (TNF)-alpha induces increases in corticotrophin releasing hormone (CRH) and CRH type 1 receptors in the hypothalamic paraventricular nucleus (PVN). In this study, we explored the hypothesis that CRH in the PVN contributes to sympathoexcitation via interaction with neurotransmitters in heart failure (HF). Sprague-Dawley rats with HF or sham-operated controls (SHAM) were treated for 4 weeks with a continuous bilateral PVN infusion of the selective CRH-R1 antagonist NBI-27914 or vehicle. Rats with HF had higher levels of glutamate, norepinephrine (NE) and tyrosine hydroxylase (TH), and lower levels of gamma-aminobutyric acid (GABA) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN when compared to SHAM rats. Plasma levels of cytokines, NE, ACTH and renal sympathetic nerve activity (RSNA) were increased in HF rats. Bilateral PVN infusions of NBI-27914 attenuated the decreases in PVN GABA and GAD67, and the increases in RSNA, ACTH and PVN glutamate, NE and TH observed in HF rats. These findings suggest that CRH in the PVN modulates neurotransmitters and contributes to sympathoexcitation in rats with ischemia-induced HF.
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