Adrenal cortex hypoxia modulates aldosterone production in heart failure

Kaoru Yamashita, Kentaro Ito, Jin Endo, Tomohiro Matsuhashi, Yoshinori Katsumata, Tsunehisa Yamamoto, Kohsuke Shirakawa, Sarasa Isobe, Masaharu Kataoka, Naohiro Yoshida, Shinichi Goto, Hidenori Moriyama, Hiroki Kitakata, Fumiko Mitani, Keiichi Fukuda, Nobuhito Goda, Atsuhiro Ichihara, Motoaki Sano*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Plasma aldosterone concentration increases in proportion to the severity of heart failure, even during treatment with renin-angiotensin system inhibitors. This study investigated alternative regulatory mechanisms of aldosterone production that are significant in heart failure. Dahl salt-sensitive rats on a high-salt diet, a rat model of heart failure with cardio-renal syndrome, had high plasma aldosterone levels and elevated β3-adrenergic receptor expression in hypoxic zona glomerulosa cells. In H295R cells (a human adrenocortical cell line), hypoxia-induced β3-adrenergic receptor expression. Hypoxia-mediated β3-adrenergic receptor expression augmented aldosterone production by facilitating hydrolysis of lipid droplets though ERK-mediated phosphorylation of hormone-sensitive lipase, also known as cholesteryl ester hydrolase. Hypoxia also accelerated the synthesis of cholesterol esters by acyl-CoA:cholesterol acyltransferase, thereby increasing the cholesterol ester content in lipid droplets. Thus, hypoxia enhanced aldosterone production by zona glomerulosa cells via promotion of the accumulation and hydrolysis of cholesterol ester in lipid droplets. In conclusion, hypoxic zona glomerulosa cells with heart failure show enhanced aldosterone production via increased catecholamine responsiveness and activation of cholesterol trafficking, irrespective of the renin-angiotensin system.

Original languageEnglish
Pages (from-to)184-189
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 2020 Mar 26


  • Cholesterol trafficking
  • Hormone-sensitive lipase
  • β3-adrenergic receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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