Dexmedetomidine produces dual α2-adrenergic agonist and α1-adrenergic antagonist actions on human isolated internal mammary artery

Objective: To investigate the direct effects of dexmedetomidine (DEX) on isolated human internal mammary artery (IMA). Design: In vitro experimental study. Setting: Cardiovascular Pharmacology Laboratory, Department of Pharmacology, Gulhane School of Medicine, Ankara, Turkey. Participants: IMA segments were obtained from 18 patients undergoing coronary artery bypass surgery. Interventions: The response in IMA was recorded isometrically by a force displacement transducer in isolated organ baths. DEX-induced contractions were tested in the presence of the alpha(2)-adrenoceptor antagonist yohimbine (10(-7) mol/L) and the alpha(1)-adrenoceptor antagonist prazosin (10(-6) M). The effect of DEX (10(-7), 10(-6), and 10(-5) mol/L) on phenylephrine (10(-9)-3 x 10(-4) mol/L)-induced contactions was also tested. Measurement and Main Results: DEX (10(-9) mol/L-3 x 10(-5) mol/L) caused contraction in IMA segments. The contraction at lower concentrations of DEX (10(-9) mol/L-3 x 10(-7) mol/L) was attenuated by yohimbine (10(-7) mol/L), whereas prazosin (10(-8) mol/L) attenuated the contractions at higher concentrations of DEX (10(-6) mol/L-3 x 10(-5) mol/L). Incubation of IMA segments with high concentrations of DEX (10(-6) mol/L and 10(-5) mol/L) caused an inhibition of phenylephrine (10(-9) mol/L-3 x 10(-4) mol/L)-induced contraction. Conclusion: These data suggest that DEX causes contraction by activating alpha(2)-adrenoceptors at lower concentrations, but it may also activate alpha(2)-adrenoceptors at higher concentrations in IMA. The action of DEX on phenylephrine-induced contraction may be related to an alpha(2)-adrenoceptor antagonistic effect produced via partial alpha(2)-adrenoceptor agonistic action.(C) 2007 Elsevier Inc. All rights reserved.