Grossmann M, Abiose A, Tangphao O, Blaschke T F, Hoffman B B
Division of Clinical Pharmacology, Stanford University Medical Center, CA 94305-5113, USA.
Clin Pharmacol Ther. 1996 Nov;60(5):554-60. doi: 10.1016/S0009-9236(96)90151-4.
Morphine has been extensively used in the treatment of pulmonary edema, and its action is believed to be mediated in part by its ability to produce peripheral venodilation. This study investigated whether opiates produce venodilation in human hand veins and explored the underlying mechanism(s). Fifteen healthy volunteers (11 men and four women) were studied with use of the dorsal hand vein compliance technique. After preconstriction with the selective alpha 1-adrenergic receptor agonist phenylephrine, dose-response curves were constructed to (1) opiate receptor agonists morphine (1 to 30 micrograms/min) or fentanyl (0.07 to 1 microgram/min), (2) a combination of morphine and the mu-opiate receptor antagonist naloxone, and (3) morphine and a combination of histamine (H1 and H2) receptor antagonists. Infusion of morphine caused venodilation in a dose-dependent manner, whereas fentanyl did not produce venodilation. Coinfusion of naloxone and morphine impaired the venodilation only slightly. Coinfusion of the H1- and H2-antagonists completely abolished the venodilatory effect of morphine. These results suggest that the venodilatory effect of morphine is mediated through histamine release and that mu-opiate receptors have little or no involvement in this process.
吗啡已被广泛用于治疗肺水肿，其作用被认为部分是通过产生外周静脉扩张的能力介导的。本研究调查了阿片类药物是否会使人手部静脉产生静脉扩张，并探讨了其潜在机制。使用手背静脉顺应性技术对15名健康志愿者（11名男性和4名女性）进行了研究。在用选择性α1肾上腺素能受体激动剂去氧肾上腺素进行预收缩后，构建了针对以下情况的剂量反应曲线：（1）阿片受体激动剂吗啡（1至30微克/分钟）或芬太尼（0.07至1微克/分钟），（2）吗啡与μ阿片受体拮抗剂纳洛酮的组合，以及（3）吗啡与组胺（H1和H2）受体拮抗剂的组合。输注吗啡以剂量依赖的方式引起静脉扩张，而芬太尼未产生静脉扩张。纳洛酮和吗啡共同输注仅轻微损害静脉扩张。H1和H2拮抗剂共同输注完全消除了吗啡的静脉扩张作用。这些结果表明，吗啡的静脉扩张作用是通过组胺释放介导的，并且μ阿片受体在该过程中几乎没有参与。
