Nebivolol, carvedilol and metoprolol do not influence cardiac Ca2+ sensitivity

It has been argued that some P-adrenoceptor antagonists may directly influence myofibrillar cross-bridge interaction in cardiac skinned fiber preparations of animal models. The present study investigates the effects of nebivolol, metoprolol and carvedilol on tension development of Triton X-100 skinned fibers obtained from human failing myocardium as well as on force of contraction and intracellular Ca2+ transient in isolated trabeculae. In skinned fiber preparations, none of the beta -adrenoceptor antagonists (10 muM) influenced Ca2+ sensitivity of tension development or maximal Ca2+ activated tension (DTmax): control: EC50 for Ca2+: 1.28 +/- 0.05 muM. DTmax: 14.09 +/- 0.59 mN/mm(2), nebivolol: 1.36 +/- 0.1 muM, 14.14 +/- 0.95 mN/mm(2); carvedilol: 1.32 +/- 0.11 muM, 13.83 +/- 0.90 mN/mm(2) metoprolol: 1.34 +/- 0.14 muM, 13.72 +/- 0.36 mN/mm(2). Simultaneous measurement of force and Ca2+ transient in the presence of the beta -adrenoceptor antagonists (3 muM) showed that the decrease in force of contraction was paralleled by a similar decrease in the intracellular Ca2+ transient. In conclusion, none of the investigated P-adrenoceptor antagonists influenced Ca2+ sensitivity of myofibrillar tension development in human failing myocardium. (C) 2001 Published by Elsevier Science B.V.