The inhibitory effects of iberiotoxin and 4‐aminopyridine on the relaxation induced by β1‐ and β2‐adrenoceptor activation in rat aortic rings

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Abstract
1 In rat aortic rings contracted by phenylephrine, the relaxation induced by isoprenaline was partly inhibited by iberiotoxin, (ibTX), tetraethylammonium, 4-aminopyridine (4-AP) and 1,9-dideoxyforskolin, but not by glibenclamide. 2 In the presence of 4-AP, 1,9-dideoxyforskolin failed to inhibit further the relaxant response to isoprenaline. Cromakalim-induced relaxation was inhibited by glibenclamide. 3 In the absence of endothelium, ibTX and 4-AP still inhibited the relaxant response to isoprenaline. 4 The inhibitory effect of ibTX on the relaxant response to isoprenaline was eliminated by pretreatment with ICI-118,551, a β2-adrenoceptor antagonist, but not by atenolol, a β1-adrenoceptor antagonist. 5 The inhibitory effect of 4-AP on the relaxation induced by isoprenaline was abolished by atenolol, but not by ICI-118, 551. 6 The inhibitory effect of ibTX on the isoprenaline-induced relaxation in the presence of atenolol was completely abolished by MDL 12,330A, an adenylate cyclase inhibitor. Further, the inhibitory effect of 4-AP on the isoprenaline-induced relaxation in the presence of ICI-118,551 was markedly reduced by MDL 12,330A. 7 The relaxation induced by dibutyryl cyclic AMP was partly inhibited by 4-AP but not by ibTX. However, in the presence of KT5720, an inhibitor of cyclic AMP-dependent protein kinase, ibTX failed to inhibit further the relaxation induced by isoprenaline. 8 These results suggest that, in rat aortic rings, Kca channels are involved in the relaxation induced by isoprenaline. In addition, Kca channels are mainly activated by β2-adrenoceptors through cyclic AMP-dependent pathways. Further, the inhibition of isoprenaline-relaxation by 4-AP may be related to the activation of β1-adrenoceptors and cyclic AMP formation.