Abstract 15140: The Brain AT1R are Responsible for Sympathoexcitation Associated with Brain MR Activation in Mice With Pressure Overload After Salt Loading
Background: Recently, we demonstrated that mice with pressure overload acquired salt sensitive sympathoexcitation through the activation of brain mineralocorticoid receptor (MR)-epithelial Na channels (ENaCs) pathway. It has been shown that brain angiotensin type 1 receptors (AT1R) contributes to sympathoexcitation in salt-sensitive hypertensive models. It is not known, however, whether AT1R is responsible for sympathoexcitation associated with the activation of brain MR-ENaCs pathway in pressure overload model with salt loading.
Hypothesis: The brain AT1 receptors is responsible for sympathoexcitation resulting from the salt loading induced activation of brain MR-ENaCs pathway.
Methods and Results: Aortic banding was performed in AT1R knockout mice (ABKO) and wild type mice (AB). Sham operation was performed as control (ShamKO and Sham). Four weeks after aortic banding, mice were fed either a high salt (8%) diet or regular salt diet for additional 4 weeks. High salt intake increased urinary norepinephrine excretion (uNE, a marker of sympathetic activity) in AB, but not in Sham. However, high salt intake did not change uNE in ShamKO or ABKO. In AB, high salt intake increased the brain MR expression, the phosphorylation of serum glucocorticoid-induced protein kinase1 (p-sgk1/sgk1, a marker of MR activity), and the brain ENaCs expression. In ABKO, however, high salt intake did not increase those expressions. The brain AT1R expression increased in AB with salt loading. Intracerebroventricular (ICV) infusion of telmisartan attenuated the salt-induced sympathoexcitation in AB. In contrast, before salt loading, the expression levels of both brain MR, p-sgk1/sgk1, and ENaCs slightly increased in ABKO, as did in AB.
Conclusion: Brain AT1R is responsible for sympathoexcitation associated with brain MR activation in mice with pressure overload after salt loading.
- © 2011 by American Heart Association, Inc.