We examined whether Ca2+ channel blockers inhibit the activation of the Ca2+-dependent
phosphatase calcineurin and the development of
cardiac hypertrophy in spontaneously hypertensive rats (SHR). We randomly divided 12-week-old SHR into three groups, one each receiving vehicle, bolus injection or continuous infusion of
nifedipine (10 mg/kg/day) from 12 to 24 weeks of age. Systolic blood pressure (BP) and heart rate were measured every week after the treatment using the tail-cuff plethysmography method. After 4, 8 and 12 weeks of treatment, 6 rats of each group were subjected to examinations that included an assay for
calcineurin activity in the heart, magnetic resonance imaging (MRI), histology and Northern blot analysis. Continuous infusion of
nifedipine consistently reduced BP, whereas bolus injection resulted in a fluctuation of BP. Continuous infusion of
nifedipine not only reduced left ventricular mass but also decreased the transverse diameter of cardiomyocytes, interstitial
fibrosis and the expression of the
atrial natriuretic peptide and
brain natriuretic peptide genes in the heart, while bolus injection of
nifedipine did not significantly attenuate any of these hypertrophic responses in SHR. The activity of
calcineurin in the heart was strongly suppressed by continuous but not bolus infusion of
nifedipine in SHR. The results indicate that continuous blockade of Ca2+ channels with
nifedipine effectively suppresses the development of
cardiac hypertrophy in SHR, possibly through inhibition of the
calcineurin activity.