Hamasaki Junichirou, Tsuneyoshi Isao, Katai Rumi, Hidaka Tatewaki, Boyle Walter A, Kanmura Yuichi
Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Anesth Analg. 2002 Jun;94(6):1434-40, table of contents. doi: 10.1097/00000539-200206000-00010.
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 alpha(1)-adrenergic antagonist prazosin. DEX markedly enhanced the high K(+) (40 mmol/L)-induced contraction, and this effect was reversed by the alpha(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 alpha(2)-adrenergic stimulants significantly inhibited the contractions elicited by the alpha(1)-adrenergic agonist phenylephrine (10(-6) mol/L) and, to a lesser extent, those elicited by the alpha(1)/alpha(2)-agonist norepinephrine (10(-6) mol/L). These results suggest the possibility that DEX and CLO each have a high affinity for alpha(1)-adrenoceptors in human isolated gastroepiploic arteries, resulting in a reduced efficacy of alpha(1)-adrenergic activation by alpha-agonists. The differing affinities of the drugs for alpha(1)- and alpha(2)-adrenoceptors may help explain their additional actions: 1) DEX enhances the high K(+)-induced contraction presumably through alpha(2)-adrenoceptor activation, and 2) CLO acts on alpha(1)-adrenoceptors as a partial agonist when present alone.
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 alpha(1)-adrenoceptor agonists.
右美托咪定（DEX）对人血管平滑肌的作用尚不清楚。我们在体外研究了其对分离的、去内皮的人胃网膜动脉的影响，并与可乐定（CLO）进行了比较。DEX对静息张力几乎没有直接影响，而CLO产生小的收缩反应，该效应被α(1)-肾上腺素能拮抗剂哌唑嗪阻断。DEX显著增强高钾（40 mmol/L）诱导的收缩，且该效应被α(2)-肾上腺素能拮抗剂育亨宾和萝芙木碱逆转，但不受哌唑嗪影响。然而，CLO对钾诱导的收缩几乎没有影响。有趣的是，两种α(2)-肾上腺素能激动剂的较高浓度（>10(-7) mol/L）均显著抑制α(1)-肾上腺素能激动剂去氧肾上腺素（10(-6) mol/L）引起的收缩，并在较小程度上抑制α(1)/α(2)-激动剂去甲肾上腺素（10(-6) mol/L）引起的收缩。这些结果提示，DEX和CLO可能对人离体胃网膜动脉中的α(1)-肾上腺素能受体均具有高亲和力，导致α-激动剂对α(1)-肾上腺素能的激活效能降低。药物对α(1)-和α(2)-肾上腺素能受体的不同亲和力可能有助于解释它们的其他作用：1）DEX可能通过激活α(2)-肾上腺素能受体增强高钾诱导的收缩，以及2）CLO单独存在时作为α(1)-肾上腺素能受体的部分激动剂起作用。
在临床实践中达到的血浆浓度通常范围（<10(-7) mol/L）内，右美托咪定可能不会直接影响人外周阻力血管中的平滑肌。然而，大剂量时，它可能增强对非肾上腺素能血管收缩激动剂的反应，同时拮抗对α(1)-肾上腺素能受体激动剂的血管收缩反应。
