Abstract 1249: Endurance Exercise Training Restores a More Normal Beta1- to Beta2 Adrenoceptor Balance in Animals Susceptible to Ventricular Fibrillation
BACKGROUND: An enhanced cardiac β2-adrenoceptor (β2-AR) and a reduced β1-adrenoceptor (β1-AR) responsiveness were noted in dogs susceptible to ventricular fibrillation (VF). Endurance exercise training restored a more normal β2-AR responsiveness and prevented VF in these animals. The effects of endurance training on β-AR expression were not determined.
METHODS: Hearts were removed from dogs with healed myocardial infarctions in which acute ischemia either induced VF (S, susceptible, n = 8) or no arrhythmias (R, resistant, n = 8). These dogs had been randomly assigned to either 10-wk exercise training (treadmill running; S n = 4, R n = 4) or a 10-wk sedentary period (S n = 4, R n = 4). Left ventricular tissueβ-AR protein and mRNA were quantified by Western Blot analysis and RT-PCR, respectively. As β2-AR are located in the caveolae, caveolin-3 was also quantified.
RESULTS: Sedentary groups: β1-AR protein levels were significantly (ANOVA P<0.05) lower (S = 53 ± 7% of R) while β2-AR protein levels were higher (S = 208 ± 59% of R) in the susceptible dogs as compared the resistant animals; β1/β2-AR protein ratio (S, 1.2 ± 0.3 vs. R, 4.1 ± 0.8). Exercise training did not change β1-AR or β2-AR protein content in resistant or β2-AR protein expression in susceptible dogs but increased β1-AR protein expression in susceptible animals (up to 67 ± 7% of R). Exercise training also reduced caveolin-3 expression in both resistant (66.4 ± 7% of R sedentary) and susceptible (59.5 ± 18.6 % of R sedentary) dogs suggesting that fewer β2-AR localized to caveolae following exercise. Finally, exercise training significantly (ANOVA P<0.01) increased β1/β2-AR mRNA ratio in the susceptible animals (trained 22.5 ± 5.4. sedentary 1.48 ± 2.1) but not the resistant dogs (trained 14.1 ± 9.2, sedentary 13.4 ± 2.6).
CONCLUSION: Exercise training can restore cardiac β-adrenoreceptor balance by increasing β1-AR expression and by the redistribution of β2-AR in the membrane (decreased caveolin-3 expression) in animals suceptible to VF. The resulting changes in β-AR intracellular signaling pathways could reduce the risk for sudden death.