title: Enhancement of post-hypoxic contractile and metabolic recovery of perfused rat hearts by dl-propranolol: possible involvement of non-beta-receptor mediated activity.
abstract: The present study was undertaken to elucidate a possible role of non-beta-receptor mediated effects in dl-propranolol-induced enhancement of post-hypoxic contractile and metabolic recovery in perfused rat hearts. The rat hearts were perfused for 30 min under reoxygenated conditions following 15 min-substrate free-hypoxic perfusion, and the cardiac performance and myocardial metabolism were examined. Hypoxia induced complete cessation of cardiac contractile force, depletion of myocardial high-energy phosphates, release of ATP metabolites and creatine kinase from the heart. Subsequent reoxygenation produced little recovery of cardiac contractile activity and tissue high-energy phosphates, further enhancement of the release of creatine kinase and the accumulation of tissue calcium. Treatment of the hypoxic hearts with dl-propranolol, d-propranolol and atenolol was performed during 5 to 15 min of hypoxic perfusion. dl-Propranolol and d-propranolol at the concentration of 45 microM elicited a significant recovery of cardiac contractile activity and restoration of myocardial high-energy phosphates. This treatment also resulted in a suppression of the release of creatine kinase and ATP metabolites and the tissue calcium accumulation observed during hypoxia and/or reoxygenation. However, such beneficial effects were not seen in hearts treated with 45 microM atenolol. dl-Propranolol and atenolol, but not d-propranolol, in a concentration of 45 microM have been shown to reveal beta-adrenoceptor blocking action. Thus, the results suggest the involvement of non-beta-receptor mediated effects of propranolol in the enhanced post-hypoxic contractile and metabolic recovery of the perfused rat heart. The non-beta-receptor mediated activity of these drugs appears to be related to their ability to suppress the maximal driving frequency of left atrial preparations.
authors.affiliation: Second Department of Internal Medicine, University of Occupational and Environmental Health of Japan, School of Medicine, Kitakyushu.
authors.forename: H
authors.initials: H
authors.lastname: Fujioka
authors.forename: S
authors.initials: S
authors.lastname: Yoshihara
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Fukumoto
authors.forename: A
authors.initials: A
authors.lastname: Kuroiwa
authors.forename: K
authors.initials: K
authors.lastname: Tanonaka
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: S
authors.initials: S
authors.lastname: Takeo
mesh_terms: D000818:Animals; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011312:Pressure; D011433:Propranolol / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
chemical_list: D010710:Phosphates; D011943:Receptors, Adrenergic, beta; D011433:Propranolol