Nebivolol, carvedilol and metoprolol do not influence cardiac Ca(2+) sensitivity.
It has been argued that some beta-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 Ca(2+) transient in isolated trabeculae. In skinned fiber preparations, none of the beta-adrenoceptor antagonists (10 microM) influenced Ca(2+) sensitivity of tension development or maximal Ca(2+) activated tension (DT(max)): control: EC(50) for Ca(2+): 1.28+/-0.05 microM, DT(max): 14.09+/-0.59 mN/mm(2); nebivolol: 1.36+/-0.1 microM, 14.14+/-0.95 mN/mm(2); carvedilol: 1.32+/-0.11 microM, 13.83+/-0.90 mN/mm(2); metoprolol: 1.34+/-0.14 microM, 13.72+/-0.36 mN/mm(2). Simultaneous measurement of force and Ca(2+) transient in the presence of the beta-adrenoceptor antagonists (3 microM) showed that the decrease in force of contraction was paralleled by a similar decrease in the intracellular Ca(2+) transient. In conclusion, none of the investigated beta-adrenoceptor antagonists influenced Ca(2+) sensitivity of myofibrillar tension development in human failing myocardium.
Bundkirchen
A
A
Labor für Herzmuskelphysiologie und Molekulare Kardiologie, Klinik III für Innere Medizin der Universität zu Köln, Joseph-Stelzmann-Strasse 9, D-50924 Cologne, (Lindenthal), Germany.
Brixius
K
K
Bölck
B
B
Mehlhorn
U
U
Bloch
W
W
Schwinger
R H
RH
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D000068577:Nebivolol; D011412:Propanolamines / Q000494:pharmacology; D016276:Ventricular Function
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D002227:Carbazoles; D004983:Ethanolamines; D011412:Propanolamines; D000068577:Nebivolol; D000077261:Carvedilol; D008790:Metoprolol; D002118:Calcium