Inhibitory effects of melatonin on vascular reactivity: possible role of vasoactive mediators
Inhibitory effects of melatonin on vascular reactivity: possible role of vasoactive mediators
复制标题
DOI：
10.1016/s1532-0456(01)00261-7
复制
发表时间：
2001-11-01
影响因子：
3.9
通讯作者：
Rahma, HHA
中科院分区：
文献类型：
--
作者：
Anwar, MM;Meki, ARMA;Rahma, HHA
褪黑激素（melatonin，MEL）是脊椎松果体的主要激素，具有多种神经生物学效应。然而，MEL对血管组织的影响仍不清楚。本研究的第一个目的是研究MEL对离体兔主动脉环的作用及其在血管对收缩剂去甲肾上腺素（NA）和苯肾上腺素（PHE）和舒张剂（乙酰胆碱和硝普钠）的反应性中的作用。此外，还检测了一氧化氮（NO）、cGMP、总钙、脂质过氧化物、超氧化物歧化酶的水平。(SOD)和谷胱甘肽（GSH）也研究了预孵育（20分钟）在MEL与和无收缩剂的兔主动脉环的组织匀浆。结果表明，MEL具有内皮依赖性血管舒张作用，并能显著增强乙酰胆碱的血管舒张作用。MEL（10（-4）M）对NA和PHE引起的主动脉环收缩反应均有明显的抑制作用。与对照组织环相比，在NA或PHE中预孵育（20 min）的主动脉环组织匀浆中，脂质过氧化物水平显著升高，而GSH水平和SOD活性显著降低。此外，NO和cGMP水平显着降低组织环预处理NA和PHE，分别。此外，总钙的水平显着增加，只有在组织环预处理NA。与单独用NA或PHE孵育的主动脉环组织相比，MEL（10（-4）M）孵育（20 min）的主动脉环组织匀浆中脂质过氧化物水平显著降低，而GSH、NO和cGMP水平以及SOD活性显著升高。MEL + PHE孵育的主动脉环中脂质过氧化物水平显著低于PHE孵育的主动脉环，而GSH、cGMP水平和SOD活性显著高于PHE孵育的主动脉环。在MEL + NA孵育的主动脉环中，脂质过氧化物和总钙的水平显着降低，而NO的水平显着高于单独NA孵育的环组织中的水平。结论：MEL具有内皮依赖性血管舒张作用，并增强乙酰胆碱诱导的内皮依赖性血管舒张作用。MEL抑制主动脉环对NA和PHE的收缩反应。这些影响可能部分是由于重新平衡促氧化剂/抗氧化剂系统，降低血管组织中的钙含量和升高NO和cGMP水平。(C)2001 Elsevier Science Inc. All rights reserved.
Melatonin (MEL), the principal hormone of the vertebral pineal gland, elicits several neurobiological effects. However, the effects of MEL on vascular tissues are still vague. The first goal of this study was to investigate the effect of MEL on isolated rabbit aortic rings and its role in the vascular reactivity to contractile agents, noradrenaline (NA) and phenylephrine (PHE) and relaxant agents (acetylcholine and sodium nitroprusside). In addition, the levels of nitric oxide (NO), cGMP, total calcium, lipid peroxides, superoxide dismutase. (SOD) and glutathione (GSH) were also investigated in tissue homogenates of rabbit aortic rings preincubated (20 min) in MEL with and without contractile agents. Our results revealed that MEL has an endothelium-dependent vaso-relaxant effect and potentiated significantly the vaso-relaxant effect of acetylcholine. Moreover, MEL (10(-4) M) had a significant inhibitory effect on the contractile responses of aortic rings to both NA and PHE. In comparison with control tissue rings, the levels of lipid peroxides were significantly increased while the levels of GSH, and SOD activities were significantly decreased in tissue homogenates of aortic rings pre-incubated (20 min) in NA or PHE. In addition, the levels of NO and cGMP were significantly lower in tissue rings pre-treated with NA and PHE, respectively. Also, the levels of total calcium were significantly increased only in tissue rings pre-treated with NA. The levels of lipid peroxides were significantly decreased, while the levels of GSH, NO and cGMP and SOD activities were significantly increased in tissue homogenates of aortic rings incubated (20 min) in MEL (10(-4) M) in comparison to ring tissues incubated in NA or PHE alone. In aortic rings incubated in MEL + PHE, the levels of lipid peroxides were significantly lower while the levels of GSH and cGMP and SOD activities were significantly higher than their levels in ring tissues incubated in PHE. In aortic rings incubated in MEL + NA, the levels of lipid peroxides and total calcium were significantly lower while the levels of NO were significantly higher than their levels in ring tissues incubated in NA alone. We conclude that MEL has an endothelium dependent vasorelaxant effect and potentiates the endothelium dependent vasorelaxation induced by acetylcholine. MEL inhibits the contractile responses of aortic rings to NA and PHE. These effects may be, in part, due to re-balancing the pro-oxidant/antioxidants system, lowered calcium content and elevated NO and cGMP levels in vascular tissue. (C) 2001 Elsevier Science Inc. All rights reserved.