Biphasic time course of the changes in aldosterone biosynthesis under high-salt conditions in dahl salt-sensitive rats

Shintaro Morizane, Fumiko Mitani, Kae Ozawa, Kentaro Ito, Tomohiro Matsuhashi, Yoshinori Katsumata, Hideyuki Ito, Xiaoxiang Yan, Ken Shinmura, Akira Nishiyama, Seijiro Honma, Takeshi Suzuki, John W. Funder, Keiichi Fukuda, Motoaki Sano

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objective-: The comorbidity of excess salt and elevated plasma aldosterone has deleterious effects in cardiovascular disease. We evaluated the mechanisms behind the paradoxical increase in aldosterone biosynthesis in relation to dietary intake of salt. Methods And Results-: Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed a high-salt diet, and plasma and tissue levels of aldosterone in the adrenal gland and heart were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry. In Dahl-S rats, we found that the delayed and paradoxical increase in aldosterone biosynthesis after the initial and appropriate response to high salt. The late rise in aldosterone biosynthesis was accompanied by upregulation of CYP11B2 expression in the zona glomerulosa and increased adrenal angiotensin II levels and renin-angiotensin system components. It preceded the appearance of left ventricular systolic dysfunction and renal insufficiency. Blockade of angiotensin AT1 receptors reversed the paradoxical increase in aldosterone biosynthesis. In contrast, Dahl-R rats maintained the initial suppression of aldosterone biosynthesis. Aldosterone levels in the heart closely paralleled those in the plasma and adrenal gland and disappeared after bilateral adrenalectomy. Conclusion-: Chronic salt overload in Dahl-S rats stimulates aberrant aldosterone production via activation of the local renin-angiotensin system in the adrenal gland, thereby creating the comorbidity of excess salt and elevated plasma aldosterone.

Original languageEnglish
Pages (from-to)1194-1203
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume32
Issue number5
DOIs
Publication statusPublished - 2012 May 1

Keywords

  • 12/15-lipoxygenase
  • Aldosterone
  • Angiotensin II
  • CYP11B2
  • Electrospray ionization
  • Gene expression
  • Liquid chromatography
  • Tandem mass spectrometry

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Morizane, S., Mitani, F., Ozawa, K., Ito, K., Matsuhashi, T., Katsumata, Y., Ito, H., Yan, X., Shinmura, K., Nishiyama, A., Honma, S., Suzuki, T., Funder, J. W., Fukuda, K., & Sano, M. (2012). Biphasic time course of the changes in aldosterone biosynthesis under high-salt conditions in dahl salt-sensitive rats. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(5), 1194-1203. https://doi.org/10.1161/ATVBAHA.111.242719