2010 Fiscal Year Final Research Report
Abnormal brain Na handling contributes to salt-induced cardiac dysfunction in heart failure model
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.
|