Effects of α_1-Adrenoreceptor Subtype Blockade on Ischemia-Reperfusion Injury

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概要

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• To clarify the roles of subclasses of α_1-adrenoreceptors in ischemic-reperfused myocardium, we compared the effect of the nonselective α_1-blocker bunazosin with that of the α_<1A>-blocker WB4101 and the α_<1B>-blocker chlorethylctonidine (CEC) in isolated rat hearts. After 30 min of preperfusion, Langendorff-perfused hearts were subjected to 25 rain of global ischemia followed by 30 min of reperfusion. Hearts were randomly divided into 4 groups, with one of the following substances being added to the perfusate: buffer alone (control), 10^<-6> mol/L bunazosin, 10^<-7> mol/L WB4101, or 10^<-7> mol/L CEC. Bunazosin had a negative inotropic effect and preserved the postischemic ATP content, reduced the postischemic increase in intracellular Na^+ content and then enhanced postreperfusion recovery of creatine phosphate. Bunazosin also reduced myocardial ^<45>Ca^<2+> uptake during reperfusion (control 5.2 vs bunazosin 2.5μmol/g dry weight of tissue (dwt), p<0.01). However, the recovery of left ventricular developed pressure (DP) was not improved when bunazosin was added to the perfusate during reperfusion. WB4101 had neither a negative inotropic nor an energy-sparing effect, but it improved the recovery of DP (control 43% vs WB4101 56% of preischemic value, p<0.05) with no reduction in myocardial ^<45>Ca^<2+> uptake. CEC had a negative inotropic and energy-sparing effect and then reduced myocardial ^<45>Ca^<2+> uptake (CEC 3.1μmol/g dwt, p<0.05), but it did not improve the recovery of DP. These results suggest that the preischemic administration of an α_<1B>-adrenoreceptor subtype blocker protected ischemic-reperfused myocardium via reduction of Ca^<2+> overload, whereas the selective blockade of the α_<1A>-adrenoreceptor subtype reduced myocardial damage via mechanism(s) other than Ca^<2+> metabolism.

• 社団法人日本循環器学会の論文
• 1997-10-20

著者

• Shinmura Ken

  Department Of Geriatric Medicine Keio University School Of Medicine

• Hasegawa Hiroshi

  Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine

• Tani Masato

  Department Of Geriatric Medicine Keio University School Of Medicine

• Tani Masato

  Cardiopulmonary Division Department Of Medicine School Of Medicine Keio University

• Asakura Yasushi

  Department Of Caridology Toyohashi Heart Center

• Asakura Yasushi

  Cardiopulmonary Division Department Of Medicine Keio University School Of Medicine

• Hasegawa Hiroshi

  Department Of Cardiovascular Science And Medicine Chiba University Graduate School Of Medicine

• NAKAMURA Yoshiro

  Department of Chemistry, Faculty of Science, Konan University

• Nakamura Yoshiro

  Geriatrics, School of Medicine, Keio University

• Nakamura Y

  Geriatrics School Of Medicine Keio University

• Nishikawa Yasuhiro

  Cardiopulmonary Division Dept. Of Med. School Of Med. Keio Univ.

• Nakamura Yoshiro

  Department Of Internal Medicine School Of Medicine Keio University

• Suganuma Yukako

  Department of Geriatric Medicine, Keio University School of Medicine

• Ebihara Yoshinori

  Departments of Geriatric Medicine, Keio University School of Medicine

• Asakura Yasushi

  Internal Medicine, Keio University School of Medicine

• Nakamura Yoshiro

  Dept. Of Intern. Med. Keio Univ. School Of Med.

• Tani Masato

  Department Of Cardiology

• Tani Masato

  Cardio-pulmonary Division School Of Medicine Keio University

• Nakamura Yoshiro

  Cardio-pulmonary Division Department Of Medicine Keio University School Of Medicine

• Nakamura Yoshiro

  Cardiopulmonary Division Department Of Medicine School Of Medicine Keio University

• Nakamura Yoshiro

  Department Of Internal Medicine Keio University Hoipital

• Asakura Yasushi

  Cardiopulmonary Division Keio University School Of Medicine

• Nishikawa Yasuhiro

  Department Of Internal Medicine School Of Medicine Keio University

• Nakamura Yoshirou

  Cardiopulmonary Division School Of Medicine Keio Univ.

• Ebihara Yoshinori

  Departments Of Geriatric Medicine Keio University School Of Medicine

• Suganuma Yukako

  Department Of Geriatric Medicine Keio University School Of Medicine

• Nishikawa Yasuhiro

  Cardiopulmonary Division Department Of Medicine Keio University School Of Medicine

• Nakamura Yoshiro

  Department Of Chemistry Faculty Of Science Konan University

• Nakamura Yoshiro

  Cardiopulmonary Division. Department Of Internal Medicine Keio University

• Asakura Yasushi

  Internal Medicine Keio University School Of Medicine

• Hasegawa Hiroshi

  Department Of Geriatric Medicine Keio University School Of Medicine

• Hasegawa Hiroshi

  Department Of Applied Physics Department Of Physics University Of Tokyo

• Nakamura Yoshirou

  Cardiopulmonary Division. Department Of Internal Medicine Keio University

• Hasegawa Hiroshi

  Department Of Adme And Toxicology For Screening Developmental Research Laboratories Shionogi & Co. Ltd.

• EBIHARA Yoshinori

  Department of Geriatric Medicine, Keio University School of Medicine

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