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

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