Effects of α1-Adrenoreceptor Subtype Blockade on Ischemia-Reperfusion Injury

To clarify the roles of subclasses of alpha(1)-adrenoreceptors in ischemic-reperfused myocardium, we compared the effect of the nonselective alpha(1)-blocker bunazosin with that of the alpha(1A)-blocker WB4101 and the alpha(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 Ca-45(2+) uptake during reperfusion (control 5.2 vs bunazosin 2.5 mu mol/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 Ca-45(2+) uptake. CEC had a negative inotropic and energy-sparing effect and then reduced myocardial Ca-45(2+) uptake (CEC 3.1 mu mol/g dwt, p<0.05), but it did not improve the recovery of DP. These results suggest that the preischemic administration of an alpha(1B)-adrenoreceptor subtype blocker protected ischemic-reperfused myocardium via reduction of Ca2+ overload, whereas the selective blockade of the alpha(1A)-adrenoreceptor subtype reduced myocardial damage via mechanism(s) other than Ca2+ metabolism.