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Brain salt sensitivity in mice with LVH is enhanced via Rho‐kinase pathway through ENaC activation
Author(s) -
ITO KOJI,
HIROOKA YOSHITAKA,
SUNAGAWA KENJI
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.609.14
Subject(s) - medicine , endocrinology , epithelial sodium channel , hyperactivation , blood pressure , chemistry , left ventricular hypertrophy , rho associated protein kinase , kinase , sodium , biochemistry , organic chemistry
Salt intake predisposes patients with left ventricular hypertrophy (LVH) to heart failure. We hypothesized that brain Na‐sensitivity increased in patients with LVH. To examine the mechanism of Na‐sensitivity associated with LVH, we performed aortic banding (AB) to produce mice with LVH. Four weeks after AB, 24‐h urinary catecholamine excretion (U‐CA) tended to increase in AB compared with sham‐operated mice (Sham). AB induced an increase in the LV wall thickness without LV dysfunction. AB was then fed either a high‐salt diet (ABH) or a regular‐salt diet (ABR) for 4 weeks. LV dysfunction and U‐CA increased in ABH compared with ABR. We then examined brain Na‐sensitivity. Intracerebroventricular (ICV) infusion of high‐Na artificial cerebrospinal fluid into AB and Sham increased U‐CA, arterial pressure, and heart rate to a greater extent in AB than in Sham. Infusion (ICV) of an epithelial Na channel (ENaC) blocker into ABH for 4 weeks significantly lowered U‐CA and improved LV function. Infusion of a Rho‐kinase inhibitor also attenuated the salt‐induced sympathetic hyperactivation and LV dysfunction in ABH. The levels of phosphorylated‐moesin, a substrate of Rho‐kinase, were significantly greater in AB than in Sham. These results suggest that increased brain Na‐sensitivity, due to the activation of ENaC via Rho‐kinase contributes to salt‐induced sympathetic hyperactivation and LV dysfunction in mice with LVH.