Author(s)

Daisuke Chino, Mai Naramatsu, Keisuke Obara, Yoshio Tanaka

Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan.

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 F_2α. 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.

Clonidine, α₂-Adrenoceptor (α₂-AR), α₁-Adrenoceptor (α₁-AR), Rat Aorta, Relaxation

Chino, D. , Naramatsu, M. , Obara, K. and Tanaka, Y. (2017) Clonidine Inhibits Phenylephrine-Induced Contraction of Rat Thoracic Aortae by Competitive Antagonism of α₁-Adrenoceptors Independent of α₂-Adrenoceptor Stimulation. Pharmacology & Pharmacy, 8, 172-188. doi: 10.4236/pp.2017.85012.