Load-induced cardiomyocyte apoptosis in cultured multicellular myocardial preparations is unaltered in presence of the beta-adrenoceptor antagonist nebivolol.
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Load-induced cardiomyocyte apoptosis in cultured multicellular myocardial preparations is unaltered in presence of the beta-adrenoceptor antagonist nebivolol. / Janssen, P M L; Zeitz, Oliver; Schumann, H; Holtz, J; Hasenfuss, G.
in: PHARMACOLOGY, Jahrgang 83, Nr. 3, 3, 2009, S. 141-147.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Load-induced cardiomyocyte apoptosis in cultured multicellular myocardial preparations is unaltered in presence of the beta-adrenoceptor antagonist nebivolol.
AU - Janssen, P M L
AU - Zeitz, Oliver
AU - Schumann, H
AU - Holtz, J
AU - Hasenfuss, G
PY - 2009
Y1 - 2009
N2 - Overload-induced heart failure is associated with enhanced apoptosis of cardiomyocytes, and increased mechanical load is an inductor of this apoptosis. It is unknown whether nebivolol, a third generation beta(1)-adrenoceptor antagonist, possesses properties that can attenuate this apoptosis. Multicellular preparations from rabbit hearts were mounted in a culture system that allows for measurement of contractile parameters over several days. Culturing these muscles on a constant high preload induces apoptosis of the cardiomyocytes. Of each heart, 1 preloaded muscle preparation was treated with nebivolol (10(-6) mol/l), 1 preloaded without continuous exposure to nebivolol (positive control) and 1 unloaded (negative control). After 48 h of continuous loaded contractions, apoptosis was assessed by TUNEL-assay to confirm that nuclei of myocytes were affected, or by DNA-ladder intensity analysis for semiquantification. Maximal twitch force development was slightly, but significantly, lower in preparations contracting in presence of nebivolol (compared to solvent) while twitch-timing parameters were similar. After 48 h of continuous contractions, no additional differences were observed between the groups regarding contractile parameters. DNA-ladder analysis showed a similar rate of apoptosis in presence of nebivolol. Nebivolol does not increase, nor decrease, the rate of load-induced cardiomyocyte apoptosis.
AB - Overload-induced heart failure is associated with enhanced apoptosis of cardiomyocytes, and increased mechanical load is an inductor of this apoptosis. It is unknown whether nebivolol, a third generation beta(1)-adrenoceptor antagonist, possesses properties that can attenuate this apoptosis. Multicellular preparations from rabbit hearts were mounted in a culture system that allows for measurement of contractile parameters over several days. Culturing these muscles on a constant high preload induces apoptosis of the cardiomyocytes. Of each heart, 1 preloaded muscle preparation was treated with nebivolol (10(-6) mol/l), 1 preloaded without continuous exposure to nebivolol (positive control) and 1 unloaded (negative control). After 48 h of continuous loaded contractions, apoptosis was assessed by TUNEL-assay to confirm that nuclei of myocytes were affected, or by DNA-ladder intensity analysis for semiquantification. Maximal twitch force development was slightly, but significantly, lower in preparations contracting in presence of nebivolol (compared to solvent) while twitch-timing parameters were similar. After 48 h of continuous contractions, no additional differences were observed between the groups regarding contractile parameters. DNA-ladder analysis showed a similar rate of apoptosis in presence of nebivolol. Nebivolol does not increase, nor decrease, the rate of load-induced cardiomyocyte apoptosis.
M3 - SCORING: Zeitschriftenaufsatz
VL - 83
SP - 141
EP - 147
IS - 3
M1 - 3
ER -
