The inhibitory effects of iberiotoxin and 4-aminopyridine on the relaxation induced by beta 1- and beta 2-adrenoceptor activation in rat aortic rings

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 beta 2-adrenoceptor antagonist, but not by atenolol, a beta 1-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 beta 2-adrenoceptors through cyclic AMP-dependent pathways. Further, the inhibition of isoprenaline-relaxation by 4-AP may be related to the activation of beta 1-adrenoceptors and cyclic AMP formation.