Effects of nebivolol on ischemia-induced metabolic changes in dog hearts

dl-Nebivolol has a beta(1)-adrenergic blocking property and l-nebivolol has an endothelial-dependent vasodilating property, sp that a racemic mixture, deltal-nebivolol, shows both properties. This study examined the effect of dl-nebivolol on ischemic myocardium in anesthetized open chest dogs. Ischemia was induced for 3 min by ligating the left anterior descending coronary artery 10 min after IV injection of vehicle, dl-nebivolol (0.03, 0.1, and 0.3 mg/kg), or d- or l-nebivolol (0.15 mg/kg). Ischemia significantly decreased the levels of ATP, creatine phosphate, and fructose-1,6-diphosphate and increased those of ADP, AMP, hexose monophosphates, and ratio of [lactate]/[pyruvate]. dl-Nebivolol at higher doses significantly attenuated some metabolic changes caused by ischemia. Although neither enantiomers significantly affected these ischemia-induced metabolic changes, d-nebivolol appeared to attenuate adenine nucleotide reduction due to ischemia. Pretreatment with Nw-nitro-l-arginine methyl ester did not abolish the restoration of ischemia-induced myocardial metabolic changes by dl-nebivolol. In conclusion, dl-nebivolol lessens ischemic derangement of myocardial metabolism, and the effects may be due mainly to its beta-adrenergic blocking property but not to endothelium-dependent vasorelaxing property.