Differential effects of carvedilol and atenolol on plasma noradrenaline during exercise in humans

AIMS: Evidence of long-term beneficial effects of beta-blockers on mortality and morbidity in patients with heart failure has been demonstrated in recent randomized trials. However, not all beta-blockers are identical. Carvedilol, a nonselective beta- and alpha-adrenergic blocker, can potentially blunt the release of noradrenaline by blocking presynaptic beta2-adrenergic receptors. To test this hypothesis, we have compared the effects of carvedilol and atenolol on plasma noradrenaline during exercise in healthy young volunteers. METHODS: This study investigated the differential effects of 2 weeks pretreatment with carvedilol 25 mg day(-1) and atenolol 50 mg day(-1) on plasma noradrenaline at rest and during exercise on a treadmill in a double-blind randomized crossover study, involving 12 healthy male volunteers (mean age 21.6 +/- 0.3 years). RESULTS: Haemodynamic parameters at rest and during exercise were not significantly different in either carvedilol or atenolol pretreatment groups. However, carvedilol pretreatment significantly blunted the increase in plasma noradrenaline during exercise [393.8 +/- 51.7 pg ml(-1) (pretreatment) to 259.7 +/- 21.2 pg ml(-1) (post-treatment)], when compared with atenolol [340.4 +/- 54.6 pg ml(-1) (pretreatment) to 396.2 +/- 32.0 pg ml(-1) (post-treatment)]. The difference between carvedilol and atenolol (95% confidence interval) was -145.2, -351.0, P < 0.05. CONCLUSIONS: We have demonstrated that carvedilol but not atenolol significantly blunted the increase in plasma noradrenaline during exercise. These findings may suggest a sympathoinhibitory effect of carvedilol that may enhance its ability to attenuate the cardiotoxicity associated with adrenergic stimulation in patients with heart failure.