Corticosterone-activated mineralocorticoid receptor contributes to salt-induced sympathoexcitation in pressure overload mice

Koji Ito, Yoshitaka Hirooka, Kenji Sunagawa

Research output: Contribution to journalArticle

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Abstract

We previously reported that pressure overload (PO) activates the hypothalamic mineralocorticoid receptor (MR) and angiotensin II type 1 receptor (AT1R). Moreover, salt intake further activates the hypothalamic MR and AT1R, resulting in salt-induced sympathoexcitation. However, the mechanism underlying this pathway activation in response to a high salt intake remains unknown. Although the role of aldosterone is extensively examined as a ligand for MR, corticosterone is able to bind to MR. Therefore, we hypothesized that corticosterone contributes to salt-induced sympathoexcitation in PO-mice. Four weeks after aortic banding to produce PO-mice, or a sham operation for controls, the mice were fed a high-salt diet for an additional 4weeks. Compared to Sham-mice, the expression levels of hypothalamic MR, serum glucocorticoid-induced kinase 1 (a marker of MR activity) and AT1R increased in PO-mice. Salt intake further increased the expression levels of these proteins only in PO-mice with the increases in sympathetic activity evaluated on the basis of the excretion of 24-h urinary norepinephrine excretion. Bilateral adrenalectomy or the intraperitoneal infusion of metyrapone, a corticosterone synthase inhibitor, attenuated salt-induced sympathoexcitation via inhibition of the hypothalamic MR and AT1R activity. These adrenalectomy-induced alterations disappeared after corticosterone replacement therapy. We also found decreased expression levels of 11β-hydroxysteroid dehydrogenase type 2, suggesting that corticosterone is apt to bind to MR. These results indicate that salt intake in PO-mice causes sympathoexcitation via, at least in part, corticosterone-induced MR and AT1R activation in the hypothalamus.

Original languageEnglish
Pages (from-to)550-556
Number of pages7
JournalClinical and Experimental Hypertension
Volume36
Issue number8
DOIs
Publication statusPublished - Jan 1 2014

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Mineralocorticoid Receptors
Corticosterone
Salts
Angiotensin Type 1 Receptor
Pressure
Adrenalectomy
Parenteral Infusions
11-beta-Hydroxysteroid Dehydrogenases
Metyrapone
Aldosterone
Glucocorticoids
Hypothalamus
Norepinephrine
Phosphotransferases
Diet
Ligands

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology

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Corticosterone-activated mineralocorticoid receptor contributes to salt-induced sympathoexcitation in pressure overload mice. / Ito, Koji; Hirooka, Yoshitaka; Sunagawa, Kenji.

In: Clinical and Experimental Hypertension, Vol. 36, No. 8, 01.01.2014, p. 550-556.

Research output: Contribution to journalArticle

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