Voluntary exercise-induced changes in β(2)-adrenoceptor signalling in rat ventricular myocytes

Regular exercise is beneficial to cardiovascular health. We tested whether mild voluntary exercise training modifies key myocardial parameters [ventricular mass, intracellular calcium ([Ca(2+)](i)) handling and the response to β-adrenoceptor (β-AR) stimulation] in a manner distinct from that reported for beneficial, intensive training and pathological hypertrophic stimuli. Female rats performed voluntary wheel-running exercise for 6–7 weeks. The mRNA expression of target proteins was measured in left ventricular tissue using real-time reverse transcriptase-polymerase chain reaction. Simultaneous measurement of cell shortening and [Ca(2+)](i) transients were made in single left ventricular myocytes and the inotropic response to β(1)- and β(2)-AR stimulation was measured. Voluntary exercise training resulted in cardiac hypertrophy, the heart weight to body weight ratio being significantly greater in trained compared with sedentary animals. However, voluntary exercise caused no significant alteration in the size or time course of myocyte shortening and [Ca(2+)](i) transients or in the mRNA levels of key proteins that regulate Ca(2+) handling. The positive inotropic response to β(1)-AR stimulation and the level of β(1)-AR mRNA were unaltered by voluntary exercise but both mRNA levels and inotropic response to β(2)-AR stimulation were significantly reduced in trained animals. The β(2)-AR inotropic response was restored by exposure to pertussis toxin. We propose that in contrast to pathological stimuli and to beneficial, intense exercise training, modulation of Ca(2+) handling is not a major adaptive mechanism in the response to mild voluntary exercise. In addition, and in a reversal of the situation seen in heart failure, voluntary exercise training maintains the β(1)-AR response but reduces the β(2)-AR response. Therefore, although voluntary exercise induces cardiac hypertrophy, there are distinct differences between its effects on key myocardial regulatory mechanisms and those of hypertrophic stimuli that eventually cause cardiac decompensation.