β-Adrenoceptor subtypes and cAMP role in adrenaline- and noradrenaline-induced relaxation in the rat thoracic aorta

Abstract

Object We identified the β-adrenoceptor (β-AR) subtypes responsible for the relaxant responses to adrenaline (AD) and noradrenaline (NA) in the rat thoracic aorta and examined the role of cAMP which is involved in these relaxant responses. Methods The effects of β-AR antagonists or the adenylyl cyclase inhibitor SQ 22,536 on AD- and NA-induced relaxant responses in phenylephrine-induced contraction and increases in cAMP levels were examined in isolated, endothelium-denuded rat thoracic aorta segments. Results AD-induced relaxation was completely suppressed by propranolol (10⁻⁷ M) or by ICI-118,551 (10⁻⁸ M) plus atenolol (10⁻⁶ M), and was also very strongly inhibited by ICI-118,551 (10⁻⁸ M) alone. AD (10⁻⁵ M) increased tissue cAMP levels by approximately 1.9-fold compared with that in non-stimulated aortic tissue, but did not significantly increase cAMP levels in the presence of ICI-118,551 (10⁻⁸ M) or SQ 22,536 (10⁻⁴ M). AD-induced relaxation was strongly suppressed by SQ 22,536 (10⁻⁴ M). NA-induced relaxation was almost completely suppressed by atenolol (10⁻⁶ M) plus ICI-118,551 (10⁻⁸ M) although it was hardly affected by ICI-118,551 (10⁻⁸ M) alone. NA (10⁻⁵ M) increased tissue cAMP levels by approximately 2.2-fold compared with that in non-stimulated aortic tissue, but did not significantly increase cAMP levels in the presence of atenolol (10⁻⁶ M) or SQ 22,536 (10⁻⁴ M). NA-induced relaxation was strongly suppressed by SQ 22,536 (10⁻⁴ M). Conclusion In rat thoracic aorta, AD- and NA-induced relaxations, which are both strongly dependent on increased tissue cAMP levels, are mainly mediated through β₂- and β₁-adrenoceptors respectively.