Calcineurin Inhibition Attenuates Mineralocorticoid-Induced Cardiac Hypertrophy

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...