Impact of beta-adrenoceptor antagonists on myofilament calcium sensitivityof rabbit and human myocardium

beta-Adrenoceptor antagonists (beta-blockers) are commonly used in clinical pharmacotherapy of cardiovascular diseases. Carvedilol and nebivolol posse ss beneficial effects on myocardial function in situations of oxidative str ess associated with intracellular calcium overload. This preservation of co ntractile function might be due to direct scavenging capacities or ttl comp ensation of the intracellular calcium overload through direct impact on myo filament calcium sensitivity. Accordingly, we measured the relation between calcium and force in the absence and in the presence of 10(-6) M carvedilo l, nebivolol, or propranolol in skinned right ventricular trabeculae of rab bit hearts. In rabbit myocardium. nebivolol (10(-6) M) altered the pCa(50%) by rightward shift (less sensitive) from 5.72 +/- 0.05 to 5.57 +/- 0.05 (p < 0.05). Maximal force development was reduced by nebivolol. In contrast, the same concentration of propranolol or carvedilol did not influence calci um sensitivity and force development. In additional experiments, we repeate d this protocol in trabeculae from human failing hearts. As in rabbit trabe culae, nebivolol shifted the pCa(50%) by 0.16 +/- 0.04 pCa units to the rig ht (p < 0.05). Experiments with intact rabbit trabeculae confirmed depresse d contractility: when all beta-adrenoceptors were blocked by 10(-6) M propr anolol, subsequent addition of 10(-6) M nebivolol reduced developed force o f these muscles significantly from 3.1 +/- 0.9 to 1.7 +/- 0.4 mN/mm(2). We conclude that nebivolol desensitizes cardiac myofilaments slightly, whereas neither propranolol nor carvedilol had an effect.