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(Circulation. 2002;105:677.)
© 2002 American Heart Association, Inc.

Brief Rapid Communication

Calcineurin Inhibition Attenuates Mineralocorticoid-Induced Cardiac Hypertrophy

Yoshiyu Takeda, MD; Takashi Yoneda, MD; Masashi Demura, MD; Mikiya Usukura, MD; Hiroshi Mabuchi, MD

From the Second Department of Internal Medicine, Kanazawa University, Kanazawa, Japan.

Correspondence to Yoshiyu Takeda, MD, Second Dept of Internal Medicine, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan. E-mail takeday{at}im2.m.kanazawa-u.ac.jp

Background— It remains unclear how mineralocorticoids induce cardiac hypertrophy and fibrosis. Recently, activation of the calcium-dependent phosphatase, calcineurin, has been shown to induce cardiac hypertrophy. In the present study, we examine the role of calcineurin in mineralocorticoid-induced cardiac hypertrophy and fibrosis.

Methods and Results— Uninephrectomized Wistar-Kyoto rats were placed on a 1.0% NaCl diet and treated with aldosterone (0.75 µg · h^-1) for 6 weeks with or without the calcineurin inhibitors, FK506 (0.5 mg · kg^-1 · d^-1) or cyclosporine A (10 mg · kg^-1 · d^-1). The effect of the angiotensin II type 1 receptor antagonist, losartan (10 mg · kg^-1 · d^-1)on aldosterone-induced cardiac hypertrophy was also studied. Treatment with aldosterone increased the heart weight/body weight ratio, cardiomyocyte size, and collagen amount. The expression of mRNA of both type-III collagen and atrial natriuretic peptide in the heart were increased by aldosterone administration. Both calcineurin activity and its mRNA expression were also increased in aldosterone-induced hypertrophic heart. Treatment with losartan, FK506, or cyclosporine partially prevented aldosterone-induced cardiac hypertrophy and fibrosis.

Conclusion— These results suggest that calcineurin is involved in the development of cardiac hypertrophy and fibrosis induced by mineralocorticoid excess. Inhibition of calcineurin may therefore prevent cardiac hypertrophy and fibrosis in mineralocorticoid hypertension.

Key Words: calcineurin • aldosterone • heart • hypertrophy • fibrosis

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