TY - JOUR
T1 - Isoproterenol-induced creatine kinase leakage in Langendorff-perfused rat heart associated with significant myocardial edema
AU - Odashiro, Keita
AU - Hiramatsu, Shin Ichi
AU - Maruyama, Toru
AU - Kaji, Yoshikazu
AU - Kanaya, Shozo
AU - Fujino, Takehiko
AU - Niho, Yoshiyuki
PY - 1998/7
Y1 - 1998/7
N2 - Since the mechanism of creatine kinase (CK) leakage induced by β-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 β-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.
AB - Since the mechanism of creatine kinase (CK) leakage induced by β-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 β-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.
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U2 - 10.1536/ihj.39.513
DO - 10.1536/ihj.39.513
M3 - Article
C2 - 9810301
AN - SCOPUS:0031872063
SN - 1349-2365
VL - 39
SP - 513
EP - 525
JO - International Heart Journal
JF - International Heart Journal
IS - 4
ER -