Caffrey J L, Gu H, Barron B A, Gaugl J F
Department of Physiology, Texas College of Osteopathic Medicine, Fort Worth 76107.
Am J Physiol. 1991 Feb;260(2 Pt 2):H386-92. doi: 10.1152/ajpheart.1991.260.2.H386.
The intravenous administration of methionine enkephalin in anesthetized dogs produces an abrupt decline in mean arterial pressure, left ventricular pressure, and the maximal rate of left ventricular pressure development. All of these changes are prevented by receptor blockade with the opiate antagonist, naloxone. To evaluate peripheral vascular contributions to these responses, experiments were conducted in a constant pressure-isolated perfused hindlimb. In this model, the sharp decline in mean arterial pressure associated with enkephalin injection (5 micrograms/kg iv) coincided with an equally sharp decline in vascular resistance (rise in blood flow) in the hindlimb. Both were blocked by naloxone pretreatment (1 mg/kg). When equal doses of enkephalin were administered directly into the femoral inflow (external iliac artery), both arterial pressure and hindlimb flow responses were all but eliminated. This observation ruled out significant direct vascular interactions in the response and indicated a site of action outside the hindlimb. Additional catheters were placed in the bracheocephalic artery and descending aorta to permit the comparison of arterial injections conducted, respectively, into the cerebral or abdominal circulations. Injections introduced into the descending aorta consistently produced the greatest response, followed by injections (in descending order of effectiveness) into the jugular, the brachiocephalic, and external iliac. The response in the hindlimb vasculature was initiated at a site somewhere between the diaphragm and terminal aorta. The vascular response to enkephalin was subsequently eliminated by blocking ganglionic transmission with the nicotinic antagonist mecamylamine. These observations suggest that the opioids probably interrupt local vasomotor traffic via opiate receptors in regional sympathetic ganglia or in the spinal cord.
在麻醉犬中静脉注射甲硫氨酸脑啡肽会导致平均动脉压、左心室压力以及左心室压力上升的最大速率急剧下降。所有这些变化都可被阿片类拮抗剂纳洛酮的受体阻断所预防。为了评估外周血管对这些反应的作用，在恒压隔离灌注后肢模型中进行了实验。在该模型中，与脑啡肽注射（5微克/千克静脉注射）相关的平均动脉压急剧下降与后肢血管阻力的同样急剧下降（血流增加）同时发生。两者均被纳洛酮预处理（1毫克/千克）阻断。当将等量的脑啡肽直接注入股动脉流入端（髂外动脉）时，动脉压和后肢血流反应几乎完全消失。这一观察结果排除了反应中显著的直接血管相互作用，并表明作用部位在后肢之外。在头臂动脉和降主动脉中放置了额外的导管，以比较分别注入脑循环或腹循环的动脉注射情况。注入降主动脉的注射始终产生最大反应，其次是注入颈静脉、头臂动脉和髂外动脉（按有效性降序排列）。后肢血管系统的反应始于横膈膜和主动脉末端之间的某个部位。随后，通过用烟碱拮抗剂美加明阻断神经节传递，消除了对脑啡肽的血管反应。这些观察结果表明，阿片类药物可能通过区域交感神经节或脊髓中的阿片受体中断局部血管运动信号传递。
