Original Article

Hypertension Research (2005) 28, 447–455; doi:10.1291/hypres.28.447

There is a Corrigendum (6 June 2016) associated with this article.

Excess Aldosterone under Normal Salt Diet Induces Cardiac Hypertrophy and Infiltration via Oxidative Stress

Kaoru Yoshida1, Shokei Kim-Mitsuyama1,2, Ryotaro Wake1, Yasuhiro Izumiya1, Yasukatsu Izumi1, Tokihito Yukimura1, Makiko Ueda3, Minoru Yoshiyama4 and Hiroshi Iwao1

  1. 1Department of Pharmacology, Osaka City University Graduate School of Medical Science, Osaka, Japan
  2. 2Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  3. 3Department of Pathology, Osaka City University Graduate School of Medical Science, Osaka, Japan
  4. 4Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Science, Osaka, Japan

Correspondence: Shokei Kim-Mitsuyama, M.D., Ph.D., Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-8556, Japan. E-mail: kimmitsu@gpo.kumamoto-u.ac.jp

Received 11 January 2005; Accepted 22 March 2005.



Aldosterone is known to play a role in the pathophysiology of some cardiovascular diseases. However, previous studies on aldosterone infusion have been mostly performed in animals receiving sodium loading and uninephrectomy, and thus the cardiac action of aldosterone alone remains to be fully clarified. The present study was undertaken to investigate the direct cardiac action of aldosterone infusion alone in rats not subjected to salt loading and uninephrectomy. Aldosterone (0.75 mug/h) was subcutaneously infused into rats via an osmotic minipump for 14 days. Aldosterone infusion, under a normal salt diet, induced only a slight increase in the blood pressure of normal rats throughout the infusion. However, aldosterone significantly induced cardiac hypertrophy, as shown by echocardiography and measurement of cardiomyocyte cross-sectional area. Furthermore, aldosterone caused not only cardiac interstitial macrophage infiltration but also cardiac focal inflammatory lesions, which were associated with an increase in cardiac monocyte chemoattractant protein-1 (MCP-1) and osteopontin mRNA. The slight elevation of blood pressure by aldosterone infusion was completely prevented by tempol, the superoxide dismutase mimetic. However, tempol failed to suppress cardiac hypertrophy, the formation of inflammatory lesions, and upregulation of cardiac MCP-1 and osteopontin by aldosterone, while N-acetylcysteine could inhibit all of them. Our data provide evidence that aldosterone alone can induce cardiac hypertrophy and severe inflammatory response in the heart, independently of blood pressure, even in the absence of salt loading or nephrectomy. Aldosterone seems to induce cardiac inflammation and gene expression via oxidative stress that is inhibited by N-acetylcysteine but not by tempol.


aldosterone, angiotensin II, cardiac hypertrophy, oxidative stress, inflammation



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