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. 2018;54(0):1-12.
doi: 10.1540/jsmr.54.1.

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

Shunsuke Shiina  1 , Ayaka Kanemura  1 , Chihiro Suzuki  1 , Fumiko Yamaki  1 , Keisuke Obara  1 , Daisuke Chino  1   2 , Yoshio Tanaka  1
Affiliations

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

Shunsuke Shiina et al. J Smooth Muscle Res. 2018.

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.

Keywords: catecholamines; rat thoracic aorta; relaxation; tissue cyclic AMP level; β-adrenoceptor (β-AR).

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Figures

Fig. 1.
Fig. 1.
Effect of various β-AR antagonists on adrenaline (AD)-induced relaxation in segments of the rat thoracic aorta. A: Effects of propranolol (10−7 M) (n = 5 for each). B: Effects of atenolol (10−6 M) (n = 8 for each). C: Effects of ICI-118,551 (10−8 M) (n = 5 for each). D: Effects of atenolol (10−6 M) + ICI-118,551 (10−8 M) (n = 5 for each). **P < 0.01: vs. control.
Fig. 2.
Fig. 2.
AD-mediated increase in tissue cAMP content in segments of the rat aorta and the inhibitory effects of β-AR antagonists and SQ 22,536 on this increase. AD: adrenaline (10−5 M); Ateno: atenolol (10−6 M); ICI: ICI-118,551 (10−8 M); SQ: SQ 22,536 (10−4 M). *P < 0.05, **P < 0.01: vs. control (cAMP content in unstimulated aorta). n = 5 for each.
Fig. 3.
Fig. 3.
Effects of SQ 22,536 on AD-induced relaxation in segments of the rat aorta. A: Effects of SQ 22,536 (10−4 M) on AD-induced relaxation in the absence of atenolol (n = 5 for each). B: Effects of SQ 22,536 (10−4 M) on AD-induced relaxation in the presence of atenolol (10−6 M) (n = 5 for each). **P < 0.01 vs. control or atenolol (10−6 M).
Fig. 4.
Fig. 4.
Effect of ICI-118,551 or atenolol plus ICI-118,551 on noradrenaline (NA)-induced relaxation in segments of the rat thoracic aorta. A: Effects of ICI-118,551 (10−8 M) (n = 6 for each). B: Effects of atenolol (10−6 M) + ICI-118,551 (10−8 M) (n = 5 for each). **P < 0.01 vs. control.
Fig. 5.
Fig. 5.
NA-mediated increase in tissue cAMP content in segments of the rat aorta and the inhibitory effects of β-AR antagonists and SQ 22,536 on this increase. NA: noradrenaline (10−5 M); Ateno: atenolol (10−6 M); ICI: ICI-118,551 (10−8 M); SQ: SQ 22,536 (10−4 M). **P < 0.01: vs. control (cAMP content in unstimulated aorta). n = 9 for NA and n = 8 for others.
Fig. 6.
Fig. 6.
Effects of SQ 22,536 on NA-induced relaxation in segments of the rat aorta (n = 5 for each). *P < 0.05 vs. control.
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