Studies on the mechanisms underlying β-adrenoceptor-mediated relaxation of rat abdominal aorta

Abstract

Mechanisms underlying β-adrenoceptor (β-AR)-mediated vascular relaxation were studied in the isolated rat abdominal aorta. In the endothelium-denuded helical preparations, a non-selective β-AR agonist isoprenaline elicited a concentration-dependent relaxation. In the absence of β-AR antagonists, isoprenaline-induced relaxation was not practically affected by an adenylyl cyclase inhibitor SQ 22,536 (300 μM), but was strongly diminished by high-KCl (80 mM). Isoprenaline-induced relaxation in the presence of SQ 22,536 was significantly diminished by iberiotoxin (IbTx, 0.1 μM), but was not affected by 4-aminopyridine (4-AP, 3 mM). Isoprenaline-induced relaxation was not also affected by SQ 22,536 (300 μM) even in the presence of CGP20712A (a β₁-selective antagonist) and ICI-118,551 (a β₂-selective antagonist) (0.1 μM for each), but was strongly diminished by high-KCl. By contrast, SQ 22,536-resistant, isoprenaline-induced relaxation in the presence of CGP20712A plus ICI-118,551 was not affected by IbTx (0.1 μM), but was inhibited significantly by 4-AP (3 mM). These results suggest that in rat abdominal aortic smooth muscle: 1) both β₁-/β₂-AR- and β₃-AR-mediated relaxations substantially involve cAMP-independent mechanisms; 2) β₁-/β₂-AR-mediated, cAMP-independent relaxant mechanisms are partly attributed to the large-conductance, Ca ²⁺-sensitive K⁺ (MaxiK, BK) channel whereas β₃-AR-mediated relaxant mechanisms are attributed to K_v channel.