Role of hypothalamic angiotensin type 1 receptors in pressure overload-induced mineralocorticoid receptor activation and salt-induced sympathoexcitation

Koji Ito, Yoshitaka Hirooka, Masatsugu Nakano, Nobuhiro Honda, Ryuichi Matsukawa, Kenji Sunagawa

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Pressure overload enhances salt-induced sympathoexcitation through hypothalamic mineralocorticoid receptor (MR)-epithelial Na channel activation. Pressure overload also increases hypothalamic angiotensin type 1 receptors (AT1R). However, the role of AT1R in pressure overload-induced MR activation and salt-induced sympathoexcitation remains unknown. Therefore, the aim of the present study was to address this question. We performed aortic banding (AB) on mice from the Institute of Cancer Research. The expression of hypothalamic MR, serum/glucocorticoid-induced protein kinase-1 (SGK-1) and AT1R increased independently of plasma renin activity at 2 or 4 weeks after AB. Next, we performed AB in AT1aR-knockout (KO) mice and c57BL6/J wild-type (WT) mice. Sham-operated (Sham) mice were used as a control. Four weeks after AB (AB-KO or AB-WT), the expression of hypothalamic MR and SGK-1 increased in both AB-WT and AB-KO compared with Sham-WT and Sham-KO, respectively. The expression of AT1R was also greater in AB-WT than in Sham-WT. In addition, mice were fed a high-salt (8%) diet for an additional 4 weeks (ABH-KO and ABH-WT). High salt loading increased the urinary excretion of norepinephrine, a marker of sympathetic activity in ABH-WT, concomitant with hypothalamic MR activation, but not in ABH-KO. These results indicate that pressure overload activated hypothalamic MR independently of AT1R. After salt intake, however, AT1R was necessary to maintain hypothalamic MR activation and salt-induced sympathoexcitation.

Original languageEnglish
Pages (from-to)513-519
Number of pages7
JournalHypertension Research
Volume36
Issue number6
DOIs
Publication statusPublished - Jun 2013

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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