Clonidine Inhibits Phenylephrine-Induced Contraction of Rat Thoracic Aortae by Competitive Antagonism of α₁-Adrenoceptors Independent of α₂-Adrenoceptor Stimulation

Abstract

Clonidine is a classically categorized α2-adrenoceptor (α 2 -AR) agonist that produces vascular contractions by stimulating arterial smooth muscle α 2 -ARs. However, clonidine inhibits α 1 -AR-mediated arterial contractions. Recently, it was suggested that repeated stimulation with clonidine induces desensitization of α 2 -ARs, thus inhibiting noradrenaline-induced smooth muscle contractions. In the present study, we examined whether clonidine-mediated inhibition of α 1 -AR contractions involves interactions with α 2 -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 pA 2 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 α 1 -ARs, which is mediated through a mechanism independent of α 2 -AR stimulation.