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

Holycross BJ, Kukielka M, Nishijima Y, Altschuld RA, Carnes CA, Billman GE. Exercise training normalizes -adrenoceptor expression in dogs susceptible to ventricular fibrillation. Am J Physiol Heart Circ Physiol 293: H2702–H2709, 2007. First published August 24, 2007; doi:10.1152/ajpheart.00763.2007.—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.