title: Isoproterenol-induced creatine kinase leakage in Langendorff-perfused rat heart associated with significant myocardial edema.
abstract: Since the mechanism of creatine kinase (CK) leakage induced by beta-adrenoceptor activation remains unclear, we studied the effects of incremental application (10(-9) to 10(-4) M) of isoproterenol (ISP) on the CK efflux from Langendorff-perfused isolated rat hearts under aerobic conditions. Tissue water content was estimated after the perfusion experiment. ISP-induced dose-dependent CK leakage was noted in a sigmoidal fashion, which showed low temperature-dependency (Q10 of 2.41), sensitivity to cepharantine (10(-6) M) and propranolol (10(-7) to 10(-6) M) without any signs of demand ischemia or oxidant stress. CK liberation was not replicated at all by maneuvers activating cAMP-dependent protein kinase (A-kinase). Myocardial edema noted in the control ISP application was ameliorated by exposure to 10(-6) M propranolol or cepharantine (i.e., significant fall in tissue water content; p < 0.05). Histological study revealed nonspecific myocardial fiber swelling and separation without any myocyte necrosis for all the perfusion groups. These results suggest that ISP-induced CK leakage in this model is not mediated by beta-adrenoceptor stimulation, subsequent A-kinase activation or related demand ischemia, but is attributed most to the direct effects of ISP augmenting sarcolemmal CK and water permeability.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Odashiro
authors.forename: S
authors.initials: S
authors.lastname: Hiramatsu
authors.forename: T
authors.initials: T
authors.lastname: Maruyama
authors.forename: Y
authors.initials: Y
authors.lastname: Kaji
authors.forename: S
authors.initials: S
authors.lastname: Kanaya
authors.forename: T
authors.initials: T
authors.lastname: Fujino
authors.forename: Y
authors.initials: Y
authors.lastname: Niho
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism*; D004487:Edema / Q000473:pathology / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008955:Models, Cardiovascular; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000187:drug effects / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
chemical_list: D000318:Adrenergic beta-Agonists; D003402:Creatine Kinase; D007545:Isoproterenol