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

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.