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Am J Physiol Heart Circ Physiol 293: H2702-H2709, 2007. First published August 24, 2007; doi:10.1152/ajpheart.00763.2007
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Exercise training normalizes beta-adrenoceptor expression in dogs susceptible to ventricular fibrillation

Bethany J. Holycross,1 Monica Kukielka,5 Yoshinori Nishijima,3 Ruth A. Altschuld,2,3 Cynthia A. Carnes,3,4 and George E. Billman3,5

1Department of Veterinary Biosciences, 2Department of Molecular and Cellular Biochemistry, 3Dorothy M. Davis Heart and Lung Research Institute, 4College of Pharmacy, and 5Department of Physiology and Cell Biology, Ohio State University, Columbus, Ohio

Submitted 3 July 2007 ; accepted in final form 23 August 2007

Previous studies demonstrated an enhanced beta2-adrenoceptor (AR) responsiveness in animals susceptible to ventricular fibrillation (VF) that was eliminated by exercise training. The present study investigated the effects of endurance exercise training on beta1-AR and beta2-AR expression in dogs susceptible to VF. Myocardial ischemia was induced by a 2-min occlusion of the left circumflex artery during the last minute of exercise in dogs with healed infarctions: 20 had VF [susceptible (S)] and 13 did not [resistant (R)]. These dogs were randomly assigned to either 10-wk exercise training [treadmill running; n = 9 (S) or 8 (R)] or an equivalent sedentary period [n = 11 (S) or 5 (R)]. Left ventricular tissue beta-AR protein and mRNA were quantified by Western blot analysis and RT-PCR, respectively. Because beta2-ARs are located in caveolae, caveolin-3 was also quantified. beta1-AR gene expression decreased (~5-fold), beta2-AR gene expression was not changed, and the ratio of beta2-AR to beta1-AR gene expression was significantly increased in susceptible compared with resistant dogs. beta1-AR protein decreased (~50%) and beta2-AR protein increased (400%) in noncaveolar fractions of the cell membrane in susceptible dogs. Exercise training returned beta1-AR gene expression to levels seen in resistant animals but did not alter beta2-AR protein levels in susceptible dogs. These data suggest that beta1-AR gene expression was decreased in susceptible dogs compared with resistant dogs and, further, that exercise training improves beta1-AR gene expression, thereby restoring a more normal beta-AR balance.

beta-adrenergic receptors; myocardial infarction; sympathetic nervous system


Address for reprint requests and other correspondence: G. E. Billman, Dept. of Physiology and Cell Biology, Ohio State Univ., 304 Hamilton Hall, 1645 Neil Ave., Columbus, OH 43210-1218 (e-mail: billman.1{at}osu.edu)






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