Load-induced cardiomyocyte apoptosis in cultured multicellular myocardial preparations is unaltered in presence of the beta-adrenoceptor antagonist nebivolol.
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.
Janssen
P M L
PM
Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio 43210-1218, USA. janssen.10@osu.edu
Zeitz
O
O
Schumann
H
H
Holtz
J
J
Hasenfuss
G
G
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D000068577:Nebivolol; D011817:Rabbits; D013314:Stress, Mechanical; D046509:Tissue Culture Techniques
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D004247:DNA