(Circulation. 2000;101:2134.)
© 2000 American Heart Association, Inc.
Brief Rapid Communication |
Calcineurin Is Activated in Rat Hearts With Physiological Left Ventricular Hypertrophy Induced by Voluntary Exercise Training
From the Department of Cardiovascular Medicine (Y.E., K.Y., M.Sonoda, N.A., M.Sata, S.S., K.T., T.A.), University of Tokyo, Tokyo, Japan, and the Department of Physiology and Biophysics (A.G., M.L.H., M.W.W.), Case Western Reserve University, Cleveland, Ohio. Present address of Antonio Gualberto is Department of Cardiovascular & Metabolic Disease, Pfizer Central Research Division, Groton, CT 06340.
Correspondence to Teruhiko Aoyagi, MD, Department of Cardiovascular Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. E-mail aoyagi-2im{at}h.u-tokyo.ac.jp
Background—Calcineurin may play a pivotal role in the signaling of cardiac hypertrophy; since this hypothesis was first put forward, controversial reports have been published using various experimental models. This study was designed to compare the physiological left ventricular hypertrophy (LVH) induced by voluntary exercise with LVH induced by aortic constriction and to determine whether calcineurin participates in the signaling of exercise-induced LVH.
Methods and Results—Wistar rats were assigned to 1 of the following 5 groups: 10 weeks of voluntary exercise (EX), a sedentary regimen, a 1-week (AC1) or 4-week (AC4) ascending aortic constriction period, or a sham operation. EX rats ran 2.4±0.7 km/day voluntarily in specially manufactured cages; this was associated with an increase of LV diastolic dimension and stroke volume. Myocardial calcineurin activity markedly increased in EX rats (46.4±8.3 versus 18.4±0.5 pmol · min-1 · mg-1 in sedentary rats; P<0.001) and in AC1 rats (44.9±6.7 versus 22.1±3.7 pmol · min-1 · mg-1 in sham-operated rats; P<0.001), but not in AC4 rats (29.0±3.4 pmol · min-1 · mg-1). Treatment with cyclosporin A completely inhibited the development of LVH in EX rats, but it only partially attenuated the development of LVH in AC4 rats.
Conclusions—Calcineurin was activated in exercise-induced physiological LVH and in the developing phase of LVH (AC1), but not in decompensated pressure-overload hypertrophy (AC4). Cyclosporin therapy for the prevention of LVH may be harmful because it does not block the development of pathological hypertrophy but rather that of favorable adaptive hypertrophy.
Key Words: exercise • hypertrophy • signal transduction
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