Morphine is an arteriolar vasodilator in man
Morphine is an arteriolar vasodilator in man
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DOI：
10.1111/j.1365-2125.2009.03364.x
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发表时间：
2009-04-01
影响因子：
3.4
通讯作者：
Bateman, D. Nicholas
中科院分区：
文献类型：
--
作者：
Afshari, Reza;Maxwell, Simon R. J.;Bateman, D. Nicholas
关于本主题的已知信息 中心点 大约 10 年来人们就认识到吗啡是人类的静脉扩张剂，并且这种作用可能与组胺释放有关。本文添加了什么 中心点 这种作用也发生在小动脉系统中，吗啡剂量下的血管舒张可能对心力衰竭患者或滥用阿片类药物的患者具有临床意义。中心点作用是由组胺释放和一氧化氮作用介导的。中心点吗啡的这种作用机制尚不清楚，但提出了血管疾病的替代治疗靶点。吗啡对动脉系统的作用机制尚不清楚。目的是报告健康受试者对动脉内吗啡的前臂血管反应及其调节。进行了三个单独的方案：（i）剂量范围； (ii) 急性耐受性； (iii) 使用静脉闭塞体积描记法对臂内吗啡输注的前臂血流 (FBF) 反应进行随机交叉机制研究。吗啡可以单独输注（研究 1 和 2），也可以与拮抗剂一起输注：纳洛酮、联合组胺 1 和组胺 2 受体阻断剂或在一氧化氮钳夹期间输注。吗啡在 30 μ g min(-1) 剂量下引起 FBF 增加 [3.25 (0.26) ml min(-1) 100 ml(-1)] [平均值 (SEM)] 在 100 剂量时加倍μg min(-1) 至 5.23 (0.53) ml min(-1) 100 ml(-1)。在整个30分钟输注期间，未观察到对50μg min(-1)吗啡的急性耐受性，FBF增加[3.96(0.35)ml min(-1)100ml(-1)](P=0.003)。抗组胺药（P = 0.008）和一氧化氮钳（P < 0.001）预处理可消除血管舒张作用，但纳洛酮不受影响。联合H1/H2阻断进行预处理的最大FBF在30分钟后为3.06 (0.48)和2.90 (0.17) ml min(-1) 100 ml(-1)，而单独吗啡则达到4.3 (0.89) ml min(-1) 100 ml(-1)。吗啡动脉内输注到前臂循环中会导致通过局部组胺调节的一氧化氮释放来舒张血管。阿片受体机制需要进一步探索。
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTcenter dot It has been recognized for about 10 years that morphine is a veno-dilator in man and that this effect may be related to histamine release.WHAT THIS PAPER ADDScenter dot This effect also occurs in the arteriolar system, with vasodilatation at doses of morphine that may have clinical relevance in patients with heart failure, or who abuse opioids.center dot The effect is mediated by histamine release and actions of nitric oxide.center dot The mechanisms of this effect of morphine are unclear, but suggest an alternative therapeutic target in vascular disease.The mechanisms of action of morphine on the arterial system are not well understood. The aim was to report forearm vascular responses, and their mediation, to intra-arterial morphine in healthy subjects.Three separate protocols were performed: (i) dose ranging; (ii) acute tolerance; (iii) randomized crossover mechanistic study on forearm blood flow (FBF) responses to intrabrachial infusion of morphine using venous occlusion plethysmography. Morphine was infused either alone (study 1 and 2), or with an antagonist: naloxone, combined histamine-1 and histamine-2 receptor blockade or during a nitric oxide clamp.Morphine caused an increase in FBF at doses of 30 mu g min(-1) [3.25 (0.26) ml min(-1) 100 ml(-1)] [mean (SEM)] doubling at 100 mu g min(-1) to 5.23 (0.53) ml min(-1) 100 ml(-1). Acute tolerance was not seen to 50 mu g min(-1) morphine, with increased FBF [3.96 (0.35) ml min(-1) 100 ml(-1)] (P = 0.003), throughout the 30-min infusion period. Vasodilatation was abolished by pretreatment with antihistamines (P = 0.008) and the nitric oxide clamp (P < 0.001), but not affected by naloxone. The maximum FBF with pretreatment with combined H1/H2 blockade was 3.06 (0.48) and 2.90 (0.17) ml min(-1) 100 ml(-1) after 30 min, whereas with morphine alone it reached 4.3 (0.89) ml min(-1) 100 ml(-1).Intra-arterial infusion of morphine into the forearm circulation causes vasodilatation through local histamine-modulated nitric oxide release. Opioid receptor mechanisms need further exploration.