2010 Fiscal Year Final Research Report

Abnormal brain Na handling contributes to salt-induced cardiac dysfunction in heart failure model

Research Project

Project/Area Number	21790730
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Circulatory organs internal medicine
Research Institution	Kyushu University
Principal Investigator	ITO Koji Kyushu University, 大学病院, 助教 (10452757)
Project Period (FY)	2009 – 2010
Keywords	心不全 / 食塩 / 脳 / Naチャネル / ミネラルコルチコイド / 交感神経活動
Research Abstract	In pressure-overload mice, high-salt intake increased 24-h urinary catecholamine excretion resulting in cardiac dysfunction, but not in Sham-mice. We focused mineralocorticoid receptor (MR), as Na channels activator and CYP-epoxyeicoatrienoic acid (EET) pathway, as Na channels inhibitor. We examined the extent/activity of brain MR and Cyp2C9 expression and 11,12-epoxyeicosatrienoic acids (EET) concentration. In Sham-mice, high-salt intake decreased MR activation, but in pressure-overload mice. ICV infusion of MR blocker attenuated the salt-induced sympathetic activation and cardiac dysfunction in pressure-overload mice. In Sham-mice, high-salt intake increased the brain cyp2C9 expression and 11,12-EET concentration but not in pressure-overload mice. These results indicate that, in mice with pressure-overload, high-salt intake increases sympathetic outflow via the activation of brain Na channels through MR activation and insufficient activation of CYP-EET pathway.