Effects of α1-adrenoreceptor subtype blockade on ischemia-reperfusion injury

Ken Shinmura, Masato Tani, Yukako Suganuma, Hiroshi Hasegawa, Yoshinori Ebihara, Yoshiro Nakamura, Yasushi Asakura

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3 Citations (Scopus)

Abstract

To clarify the roles of subclasses of α1-adrenoreceptors in ischemic- reperfused myocardium, we compared the effect of the nonselective α1- blocker bunazosin with that of the α(1A)-blocker WB4101 and the α(1B)- blocker chlorethylclonidine (CEC) in isolated rat hearts. After 30 min of preperfusion, Langendorff-perfused hearts were subjected to 25 min 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 45Ca2+ uptake during reperfusion (control 5.2 vs bunazosin 2.5 μmol/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 45Ca2+ uptake. CEC had a negative inotropic and energy-sparing effect and then reduced myocardial 45Ca2+ uptake (CEC 3.1 μmol/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 Ca2+ overload, whereas the selective blockade of the α(1A)-adrenoreceptor subtype reduced myocardial damage via mechanism(s) other than Ca2+ metabolism.

Original languageEnglish
Pages (from-to)927-935
Number of pages9
JournalJAPANESE CIRCULATION JOURNAL
Volume61
Issue number11
DOIs
Publication statusPublished - 1997 Nov 1

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Keywords

  • Ca overload
  • Myocardial ischemia
  • Reperfusion injury
  • α-Adrenoreceptors
  • α-Subtype

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Shinmura, K., Tani, M., Suganuma, Y., Hasegawa, H., Ebihara, Y., Nakamura, Y., & Asakura, Y. (1997). Effects of α1-adrenoreceptor subtype blockade on ischemia-reperfusion injury. JAPANESE CIRCULATION JOURNAL, 61(11), 927-935. https://doi.org/10.1253/jcj.61.927