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.
Satoh
Kumi
K
Department of Pharmacology, Hokkaido College of Pharmacy, Otaru, Japan.
Takeda
Susumu
S
Kaneta
Shigeru
S
Inagami
Tadashi
T
Ichihara
Kazuo
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D050260:Carbohydrate Metabolism; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D000068577:Nebivolol; D019289:Pyruvic Acid / Q000378:metabolism; D013237:Stereoisomerism; D014664:Vasodilation / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D000068577:Nebivolol; D019344:Lactic Acid; D019289:Pyruvic Acid; D019331:NG-Nitroarginine Methyl Ester