Antiarrhythmic effects of nebivolol in experimental models in vivo.
Antiarrhythmic effects of nebivolol, a cardioselective beta 1-adrenoceptor blocker facilitating vascular release of nitric oxide (NO), were investigated in different experimental models. In the reperfusion-induced arrhythmias after 5 min of left coronary artery ligation in rats, nebivolol 1.25 mg/kg intravenously (i.v.) reduced the incidence of ventricular tachycardia (VT) from 85% in the solvent group to 33% (p < 0.05) and decreased that of ventricular fibrillation (VF) to 20% vs. 67% in the solvent group, (p < 0.05). In ischemia-induced arrhythmias resulting from 20-min coronary artery ligation in rats, nebivolol 1.25 mg/kg i.v. reduced the incidence of VT to 50% as compared with 87% in the solvent group and decreased the incidence of VF to 17% as compared with 67% in the solvent group (p < 0.05). In electrically stimulated hearts in open-chest guinea pigs, nebivolol produced a dose-dependent (0.16-2.5 mg/kg i.v.) increase in VF threshold (VFT). In guinea pigs with ouabain-induced cardiotoxicity, nebivolol 1.25 mg/kg i.v. (n = 7) doubled the doses of ouabain required to provoke toxic ECG changes as compared with those in the solvent-pretreated group. In rats with aconitine-induced cardiac toxicity, nebivolol 1.25 mg/kg i.v. significantly reduced the incidence of ventricular arrhythmias. Our results demonstrate that nebivolol suppresses arrhythmias in various experimental models in vivo.
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Department of Cardiovascular and Pulmonary Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Remeysen
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De Clerck
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D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D001578:Benzopyrans / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D008955:Models, Cardiovascular; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D000068577:Nebivolol; D010042:Ouabain / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D010042:Ouabain