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

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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.