Protective role of nebivolol in hydroxyl radical induced injury.
Increased oxidative stress has been postulated as one of the main mechanisms underlying stunned myocardium, and may play an important role in and during development of heart failure. Pharmacological interventions may attenuate or prevent detrimental effects of oxygen free radicals on the myocardium. Nebivolol has been shown to attenuate contractile dysfunction in hydroxyl radical mediated injury, but the mechanism(s) remain unknown. It was investigated whether nebivolol could partly attenuate the contractile dysfunction through a direct effect on the myofilaments. In demembranized muscles from explanted human hearts, nebivolol induced a slight desensitization of the myofilaments to calcium. Therefore, during the calcium overload that occurs during reperfusion after an ischemic event, the contractile dysfunction is less severe in the presence of nebivolol. We conclude that the protection of nebivolol in hydroxyl radical induced contractile dysfunction is mediated in part through a direct effect on the myofilaments, in addition to the previously shown preservation of sarcoplasmic reticulum function.
Janssen
P M
PM
Department of Cardiology and Pneumology, University of Göttingen, Germany.
Zeitz
O
O
Rahman
A
A
Hasenfuss
G
G
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D000068577:Nebivolol; D016877:Oxidants / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D016877:Oxidants; D000068577:Nebivolol; D017665:Hydroxyl Radical; D011433:Propranolol; D006861:Hydrogen Peroxide; D002118:Calcium