This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Hamasaki, J. Articles by Kanmura, Y. Search for Related Content PubMed PubMed Citation Articles by Hamasaki, J. Articles by Kanmura, Y. Related Collections Cardiovascular Pharmacology

---

CARDIOVASCULAR ANESTHESIA

Dual ₂-Adrenergic Agonist and ₁-Adrenergic Antagonist Actions of Dexmedetomidine on Human Isolated Endothelium-Denuded Gastroepiploic Arteries

Junichirou Hamasaki, MD^*, Isao Tsuneyoshi, MD^*, Rumi Katai, MD^*, Tatewaki Hidaka, MD^*, Walter A. Boyle, MD, and Yuichi Kanmura, MD^*

*Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, Japan; and Research Unit and Division of Critical Care, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri

Address correspondence and reprint requests to Junichirou Hamasaki, MD, Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. Address e-mail to hamasak1{at}m2.kufm.kagoshima-u.ac.jp

The actions of dexmedetomidine (DEX) on human vascular smooth muscle are unclear. We investigated its effects on isolated, endothelium-denuded human gastroepiploic arteries in vitro and compared them with clonidine (CLO). DEX had little direct effect on resting tension, whereas CLO produced small contractile responses, an effect which is blocked by the ₁-adrenergic antagonist prazosin. DEX markedly enhanced the high K⁺ (40 mmol/L)-induced contraction, and this effect was reversed by the ₂-adrenergic antagonists yohimbine and rauwolscine but unaffected by prazosin. However, CLO had little effect on the K⁺ contractions. Interestingly, larger concentrations (>10^-7 mol/L) of both ₂-adrenergic stimulants significantly inhibited the contractions elicited by the ₁-adrenergic agonist phenylephrine (10^-6 mol/L) and, to a lesser extent, those elicited by the ₁/₂-agonist norepinephrine (10^-6 mol/L). These results suggest the possibility that DEX and CLO each have a high affinity for ₁-adrenoceptors in human isolated gastroepiploic arteries, resulting in a reduced efficacy of ₁-adrenergic activation by -agonists. The differing affinities of the drugs for ₁- and ₂-adrenoceptors may help explain their additional actions: 1) DEX enhances the high K⁺-induced contraction presumably through ₂-adrenoceptor activation, and 2) CLO acts on ₁-adrenoceptors as a partial agonist when present alone.

IMPLICATIONS: Dexmedetomidine may not directly affect smooth muscle in human peripheral resistance vessels within the usual range of plasma concentrations (<10^-7 mol/L) achieved in clinical practice. However, in large doses, it could enhance the response to nonadrenergic vasoconstrictor agonists while antagonizing the vasoconstrictor response to ₁-adrenoceptor agonists.

This article has been cited by other articles:

				T. Yoshitomi, A. Kohjitani, S. Maeda, H. Higuchi, M. Shimada, and T. Miyawaki Dexmedetomidine Enhances the Local Anesthetic Action of Lidocaine via an {alpha}-2A Adrenoceptor Anesth. Analg., July 1, 2008; 107(1): 96 - 101. [Abstract] [Full Text] [PDF]

				M. Onomoto, I. Tsuneyoshi, A. Yonetani, S. Suehiro, K. Matsumoto, R. Sakata, and Y. Kanmura Differential Pharmacologic Sensitivities of Phosphodiesterase-3 Inhibitors Among Human Isolated Gastroepiploic, Internal Mammary, and Radial Arteries Anesth. Analg., October 1, 2005; 101(4): 950 - 956. [Abstract] [Full Text] [PDF]

				S. Masuki, F. A. Dinenno, M. J. Joyner, and J. H. Eisenach Selective {alpha}2-adrenergic properties of dexmedetomidine over clonidine in the human forearm J Appl Physiol, August 1, 2005; 99(2): 587 - 592. [Abstract] [Full Text] [PDF]