| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
Recently, we demonstrated that salt intake leads to sympathoexcitation due to the activation of the hypothalamic epithelial sodium channels (ENaCs) in heart failure. The aim of the present study was to clarify the mechanism of ENaCs activation in heart failure. The cardiac sympathetic afferent (CSA) is stimulated in heart failure, therefore we stimulated the CSA in mice by epicardial application of capsaicin. The capsaicin treatment upregulated the expression levels of the hypothalamic αENaCs with the increase in TNF-α. Arterial pressure (AP) and heart rate (HR) were increased by intracerebroventricular infusion of a high-Na-containing artificial cerebrospinal fluid in capsaicin-treated mice compared to that in control mice. In addition, the salt diet augmented AP, HR in capsaicin-treated mice but not in control mice. We show that CSA stimulation leads to an upregulation of hypothalamic ENaCs mediated via an increase in TNF-α and results in increased salt sensitivity.
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