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 α2-adrenoceptor antagonist yohimbine (10−7 mol/L) and the α1-adrenoceptor antagonist prazosin (10−8 M). The effect of DEX (10−7, 10−6, and 10−5 mol/L) on phenylephrine (10−9-3 × 10−4 mol/L)-induced contactions was also tested.Measurement and Main Results: DEX (10−9 mol/L-3 × 10−5 mol/L) caused contraction in IMA segments. The contraction at lower concentrations of DEX (10−9 mol/L-3 × 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 × 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 × 10−4 mol/L)-induced contraction.Conclusion: These data suggest that DEX causes contraction by activating α2-adrenoceptors at lower concentrations, but it may also activate α1-adrenoceptors at higher concentrations in IMA. The action of DEX on phenylephrine-induced contraction may be related to an α1-adrenoceptor antagonistic effect produced via partial α1-adrenoceptor agonistic action.