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Exercise training normalizes -adrenoceptor expression in dogs susceptible to ventricular fibrillation

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 ₂-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 ₁-AR and ₂-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 -AR protein and mRNA were quantified by Western blot analysis and RT-PCR, respectively. Because ₂-ARs are located in caveolae, caveolin-3 was also quantified. ₁-AR gene expression decreased (5-fold), ₂-AR gene expression was not changed, and the ratio of ₂-AR to ₁-AR gene expression was significantly increased in susceptible compared with resistant dogs. ₁-AR protein decreased (50%) and ₂-AR protein increased (400%) in noncaveolar fractions of the cell membrane in susceptible dogs. Exercise training returned ₁-AR gene expression to levels seen in resistant animals but did not alter ₂-AR protein levels in susceptible dogs. These data suggest that ₁-AR gene expression was decreased in susceptible dogs compared with resistant dogs and, further, that exercise training improves ₁-AR gene expression, thereby restoring a more normal -AR balance.

-adrenergic receptors; myocardial infarction; sympathetic nervous system

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