摘要
目的 利用ETA与M受体的相似性和差异性 ,设计合成吗啉环和哌嗪环类新结构化合物 ,分析其对血管舒张功能的影响。方法 采用离体大鼠胸主动脉环 ,观察化合物对血管张力的影响 ;并观察L NAME ,吲哚美辛和阿托品对血管环最大舒张率的影响。结果 81个化合物中有 57个能舒张血管 ,其中 8个最大舒张率在 50 %～ 85 % ;活性化合物按母核可分为 8类 ;DMHPPP和PPVP诱发的内皮依赖性舒血管反应可被L NAME和吲哚美辛所拮抗 ,但不被阿托品拮抗 ;DMHPPP和PPVP还能显著增强乙酰胆碱 (ACh)诱发的内皮依赖性舒血管反应的最大舒张率。结论 具有舒血管作用的活性化合物通过促进内皮细胞释放一氧化氮(NO)和前列环素 (PGI2 )共同实现舒张效应 ;
AIM Our investigation is to screen bioactive novel compounds using the isolated rat aortic rings and depending on the similar and distinct characteristics between the endothelial target for acetylcholine(ETA) and muscarinic receptors and to investigate the mechanisms of vasodilatory effects of candidate compounds. METHODSIn isolated rat aorta precontracted with NE, the vasodilatory effects of novel structure compounds were investigated. We Compared the maximal relaxation of endothelium denuded aorta with that of the endothelium intact aorta elicited by the 8 candidate compounds respectively. The aortas were precubated with L NAME, indomethacine and atropine before using NE, and measured the changes of the maximum vasodilatory rate of candidate compound. RESULTS AND CONCLUSION Among 81 compounds, we found 8 novel compounds which induced relaxation. Their maximal relaxation rates ranged of from 50 percent to 85 percent. The endothelium dependent relaxation induced by DMHPPP and PPVP was blocked by indomethacin and L NAME, but not by atropine. DMHPPP and PPVP also enhanced the maximal endothelium dependent relaxation induced by acetylcholine. These suggest that novel compounds may regulate functions of endothelial cell target for acetylcholine(ETA) to induce relaxation of isolated rat aortic rings, which may involve the prostacycline and nitric oxide pathways.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2003年第7期754-758,共5页
Chinese Pharmacological Bulletin
基金
国家重点基础研究发展规划 ("973")项目 (NoG19980 5112:血管内皮细胞保护作用新靶标及其先导结构的发现和优化 )
北京赛德维康医药研究院新药研究基金项目(心脑血管疾病治疗药物发现与发展研究 )资助
关键词
血管内皮细胞
M受体
乙酰胆碱靶标
一氧化氮
前列环素
阿托品
endothelial cells
muscarinic receptors
endothelial cell target for acetylcholine
nitric oxide
prostacycline
atropine
