Infarct Size-Reducing Effect of Ischemic Preconditioning Is Related to α1b-Adrenoceptors But Not to α1a-Adrenoceptors in Rabbits

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Abstract
In rabbits and rats, both stimulation of α1-adrenoceptors and ischemic preconditioning (PC) reduce infarct size. Activation of α1b-adrenoceptors play an important role in the PC effect on ventricular function in rats. However, the α1-adrenoceptors have not been reported to be related to the PC effect in rabbits, because the infarct size-reducing effect of PC is not blocked by the nonselective α-adrenoceptor antagonist, phenoxybenzamine (POB) or by the α1-adrenoceptor antagonist, BE2254. However, we speculated that α1b-adrenoceptors but not α1a-adrenoceptors may be related to the infarct size-reducing effect of PC in rabbit hearts. Thus we examined in rabbits whether the α1b-adrenoceptor blocker chloroethyl-clonidine (CEC), the α1a-adrenoceptor blocker 5-methylurapidil (5-MU), the selective α1-adrenoceptor antagonist bunazosin (BN), and the nonselective α-adrenoceptor antagonist phenoxybenzamine (POB) can block the PC effect on infarct size. Eighty-eight anesthetized open-chest Japanese white male rabbits were subjected to 30-min coronary occlusion and 48-h reperfusion. In five PC groups, the rabbits were subjected to a single 5-min occlusion and 5-min reperfusion before 30-min sustained ischemia. In the PC groups, those with CEC (3 mg/kg, n = 10), 5-MU (3 mg/kg, n = 10), BN (0.3 mg/kg, n = 10), POB (4 mg/kg, n = 10), or placebo saline (n = 10) were pretreated before PC. In the non-PC groups, those with CEC (3 mg/kg, n = 7), 5-MU (3 mg/kg, n = 7), BN (0.3 mg/kg, n = 7), POB (4 mg/kg, n = 7), or placebo saline (n = 10) were pretreated before 30-min sustained ischemia. After a 48-h reperfusion, the infarct size was measured histologically and expressed as a percentage of the area at risk. PC caused a marked reduction of infarct size as compared with the non-PC control (10 ± 3% vs. 42 ± 2%; p < 0.05). The PC effect was completely blocked by CEC (36 ± 2%) and by BN (42 ± 4%) but not by 5-MU (14 ± 1%) or POB (13 ± 2%). None of the drugs by itself affected the infarct size. Stimulation of α1b-adrenoceptors but not of α1a-adrenoceptors during PC plays an important role in the PC effect on infarct size. This may explain the previous confusion concerning the PC blocking effect of various α1-blockers.

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