Blockade of mineralocorticoid receptors improves salt-induced left-ventricular systolic dysfunction through attenuation of enhanced sympathetic drive in mice with pressure overload

Koji Ito, Yoshitaka Hirooka, Kenji Sunagawa

研究成果: ジャーナルへの寄稿記事

22 引用 (Scopus)

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Objectives: In a pressure overload model, sympathetic activity is augmented in response to salt intake. Mineralocorticoid receptors and epithelial Na channels (ENaCs) are thought to contribute to Na-processing, but the underlying mechanism is unknown. Here, we investigated the contribution of the brain mineralocorticoid receptor-ENaC pathway to salt-induced sympathetic activation in a pressure overload model. Methods and results: Aortic banding was performed to produce a mouse pressure overload model. Four weeks after aortic banding (AB-4), left-ventricular (LV) wall thickness was increased without a change in percentage fractional shortening (%FS). Sympathetic activity increased in response to a 5-day high-salt diet in AB-4, but not in Sham-4. Brain mineralocorticoid receptor, αENaC, and angiotensin II type 1 receptor (AT1R) expression levels were greater in AB-4 than in Sham-4. The increase in sympathetic activity and in the expression of these proteins was blocked by intracerebroventricular (ICV) infusion of eplerenone, a mineralocorticoid receptor blocker. In another protocol, AB-4 mice were fed a high-salt diet (AB-H) for 4 additional weeks. At 4 weeks, %FS was decreased and sympathetic activity was increased in AB-H compared with Sham. Expression of mineralocorticoid receptors and AT1R in the brain was higher in AB-H than in Sham. ICV infusion of eplerenone in AB-H attenuated salt-induced sympathoexcitation and the decreased %FS. ICV infusion of eplerenone also decreased brain AT1R expression. CONCLUSIONS: These findings indicate that activation of brain αENaC and AT1R through mineralocorticoid receptors contributes to the acquisition of Na sensitivity to induce sympathoexcitation. Therefore, high salt intake accelerates sympathetic activation and LV systolic dysfunction in a pressure overload model.

元の言語英語
ページ(範囲)1449-1458
ページ数10
ジャーナルJournal of hypertension
28
発行部数7
DOI
出版物ステータス出版済み - 7 1 2010

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All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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