Clonidine Inhibits Phenylephrine-Induced Contraction of Rat Thoracic Aortae by Competitive Antagonism of α<sub>1</sub>-Adrenoceptors Independent of α<sub>2</sub>-Adrenoceptor Stimulation

• 作者: Daisuke Chino Keisuke Obara Mai Naramatsu Yoshio Tanaka
• 来源期刊: 药理与制药(英文)
• 学科: 医学
• 关键词: CLONIDINE α2-Adrenoceptor (α2-AR) α1-Adrenoceptor (α1-AR) RAT Aorta Relaxation
• 年，卷（期）: 2017,（5）
• 页码范围: 172-188
• 页数: 17页
• 分类号: R5

摘要

Clonidine is a classically categorized α2-adrenoceptor (α2-AR) agonist that produces vascular contractions by stimulating arterial smooth muscle α2-ARs. However, clonidine inhibits α1-AR-mediated arterial contractions. Recently, it was suggested that repeated stimulation with clonidine induces desensitization of α2-ARs, thus inhibiting noradrenaline-induced smooth muscle contractions. In the present study, we examined whether clonidine-mediated inhibition of α1-AR contractions involves interactions with α2-ARs in rat thoracic aortae. 1) Clonidine and guanfacine inhibited electrical field stimulation-induced contractions in a concentration-dependent, yohimbine-sensitive manner in isolated rat vas deferens preparations. 2) Clonidine almost completely suppressed phenylephrine-induced sustained contractions of rat thoracic aortae. 3) Clonidine competitively inhibited phenylephrine-induced contractions with a pA2 value of 6.77 at concentrations between 10-7 and 10-6 M. At 10-5 M, clonidine inhibited phenylephrine-induced contractions and dramatically reduced maximum contractions. 4) In contrast, clonidine did not inhibit contractions produced by high KCl or prostaglandin F2α. 5) Inhibition of phenylephrine-induced sustained contractions by clonidine was also produced in the presence of yohimbine. However, guanfacine did not inhibit phenylephrine-induced sustained contractions. These findings suggest that clonidine inhibits phenylephrine-induced contraction of rat thoracic aortae by competitive antagonism of α1-ARs, which is mediated through a mechanism independent of α2-AR stimulation.