双模式dihydropyridine钙拮抗剂的作用:一氧化氮的作用。
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亚Dhein年代,萨拉梅赫,Berkels R,克劳斯·W
双模式dihydropyridine钙拮抗剂的作用:一氧化氮的作用。
药。1999年9月,58 (3):397 - 404。
- PubMed ID
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10493269 (在PubMed]
- 文摘
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Dihydropyridine钙拮抗剂已经使用了许多年的心绞痛和高血压的治疗。根据共同的观点,其作用机理是基于平滑肌l型钙电流的抑制,从而减少细胞内钙离子浓度和诱导平滑肌肉放松。然而,近年来证据积累了,除了这些代理的平滑肌作用,其对内皮的影响也必须考虑在内。这是表明dihydropyridines可以诱导释放血管内皮一氧化氮(NO)的各种船只和在不同的物种。这是第一次,冈瑟和他的同事们通过分析高铁血红蛋白形成的完整的内皮(猪冠状动脉)和没有与nitrendipine治疗。这些发现后来证实了直接测量或亚硝酸盐的生产。此外,在几个准备,包括微,macrovasculature vasorelaxing的敏感性的影响dihydropyridines NO-synthase抑制剂,如L-N (G) -nitroarginine (LNNA)或L-N-nitro-arginine-methyl-ester (L-NAME),已被证明。与这些研究很明显,NO-releasing效应不是nitrendipine独有而是一组共享的现象dihydropyridines和几个nondihydropyridine钙拮抗剂。除了对血管内皮细胞的作用,没有释放血小板硝苯地平也被检测到。也有研究表明长期的影响涉及没有释放的钙拮抗剂。 Regarding the underlying mechanism of NO release, nitrendipine was shown, not to decrease but to increase intracellular Ca2+ in cultured endothelial cells. This increase was sensitive to both Ca2+-free extracellular superfusion and to gadolinium, a lanthanide known to inhibit shear-stress activated cation channels. This increase in intracellular calcium can activate endothelial NO-synthase, thus inducing the release of NO. These findings on a dual mode of action, i.e. the direct relaxing effect by inhibition of the smooth muscle L-type calcium current and indirect relaxing effect by release of NO from vascular endothelium may help to understand the beneficial antihypertensive effects of the dihydropyridine calcium antagonists and the preferential effect of certain drugs in certain vascular regions (resistance versus conductive vessels). In addition, NO release from both vascular endothelium and platelets may contribute to the antiatherosclerotic and antithrombotic effects described for certain dihydropyridines.
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