%0 Journal Article
%T Clonidine Inhibits Phenylephrine-Induced Contraction of Rat Thoracic Aortae by Competitive Antagonism of ¦Á<sub>1</sub>-Adrenoceptors Independent of ¦Á<sub>2</sub>-Adrenoceptor Stimulation
%A Daisuke Chino
%A Mai Naramatsu
%A Keisuke Obara
%A Yoshio Tanaka
%J Pharmacology & Pharmacy
%P 172-188
%@ 2157-9431
%D 2017
%I Scientific Research Publishing
%R 10.4236/pp.2017.85012
%X Clonidine is a classically categorized ¦Á2-adrenoceptor (¦Á<sub>2</sub>-AR) agonist that produces vascular contractions by stimulating arterial smooth muscle ¦Á<sub>2</sub>-ARs. However, clonidine inhibits ¦Á<sub>1</sub>-AR-mediated arterial contractions. Recently, it was suggested that repeated stimulation with clonidine induces desensitization of ¦Á<sub>2</sub>-ARs, thus inhibiting noradrenaline-induced smooth muscle contractions. In the present study, we examined whether clonidine-mediated inhibition of ¦Á<sub>1</sub>-AR contractions involves interactions with ¦Á<sub>2</sub>-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<sub>2</sub> value of 6.77 at concentrations between 10<sup>-7</sup> and 10<sup>-6</sup> M. At 10<sup>-5</sup> 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<sub>2¦Á.</sub> 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 ¦Á<sub>1</sub>-ARs, which is mediated through a mechanism independent of ¦Á<sub>2</sub>-AR stimulation.
%K Clonidine
%K ¦Á&lt
%K sub&gt
%K 2&lt
%K /sub&gt
%K -Adrenoceptor (¦Á&lt
%K sub&gt
%K 2&lt
%K /sub&gt
%K -AR)
%K ¦Á&lt
%K sub&gt
%K 1&lt
%K /sub&gt
%K -Adrenoceptor (¦Á&lt
%K sub&gt
%K 1&lt
%K /sub&gt
%K -AR)
%K Rat Aorta
%K Relaxation
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=76318