内吗啡肽及其类似物对心血管系统的作用  

EFFECTS OF ENDOMORPHINS AND THEIR ANALOGS ON CARDIOVASCULAR SYSTEM

作　　者：吴宁[1] 任维华[1] 霍笑风[1] 陈强[1] 王锐[1] 

机构地区：[1]兰州大学生命科学学院生物化学与分子生物学系,甘肃兰州730000

出　　处：《药学学报》2001年第4期241-245,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金 (2 0 0 72 0 14 ) ;教育部跨世纪优秀人才培养计划基金 ;教育部重点科研基金! (0 0 2 2 ) ;甘肃省科技攻关项目

摘　　要：目的　研究内吗啡肽 (EMs)及其类似物对心血管系统的影响 ,初步探讨其作用机理。方法　测定EMs及其类似物对大鼠平均动脉压和后肢血管阻力、蟾蜍肠系膜微动脉内径、兔离体胸主动脉条张力的影响。结果　EMs及其类似物剂量依赖 ( 10 -9- 10 -6mol·L-1,iv)且Nx敏感地降低麻醉大鼠平均动脉压、后肢血管灌流压和扩张蟾蜍肠系膜微动脉。EMs对去内皮兔离体胸主动脉条张力无影响 ;但剂量依赖地显著降低完整内皮胸主动脉条张力并被Nx和L NNA阻断。结论　EMs及其类似物通过降低外周阻力而显著降低动脉血压 。AIM To analyze the effects of endomorphins (EMs) and their analogs ([ D Pro 2]EM 1, [ D Ala 2]EM 1, [ D Pro 2]EM 2 and [ D Ala 2]EM 2) on the cardiovascular system of anesthetized rats and to study its mechanism. METHODS Responses to EMs and their analogs were investigated in the systemic vascular bed of rats and the mesenteric microarteria of Bufo gargarizans . Responses to EMs were investigated on the hindquarters of the rat vascular bed under constant flow conditions and on the isolated rabbit thoracic aorta strips. RESULTS The EMs and their analogs showed dose related (10 -9 -10 -6 mol·L -1 , iv) and naloxone sensitive (2 mg·kg -1 , iv) hypotension in mean arterial pressure of rats with similar duration and vasodilatation in mesenteric microarteria of Bufo gargarizans . The sequence of potencies was EMs > [ D Pro 2]EM 2 > [ D Ala 2]EM 2 > [ D Ala 2]EM 1 > [ D Pro 2]EM 1. EMs were shown not to relax the isolated rabbit thoracic aorta strips without endothelium. EMs, however, relaxed them with endothelium significantly. This action was blocked by Nx (10 -5 mol·L -1 ) and L NNA (10 -4 mol·L -1 ). CONCLUSION The significant hypotensive activity of EMs and their analogs is mainly associated with their vasodilatation, which is related to the release of NO from vascular endothelium, and their potency is not completely related to their affinity for μ opiate receptor.

关 键 词：内吗啡肽 降血压 内皮依赖性 构效关系 类似物 心血管系统 

分 类 号：R972.4[医药卫生—药品] R541[医药卫生—药学]