盐酸埃他卡林对血管内皮细胞分泌功能的影响  

Effects of iptakalim hydrochloride on secretion function of blood vessel endothelial cells

作　　者：贾国栋[1] 刘国树[1] 汪海[2] 

机构地区：[1]解放军总医院南楼心肾科,北京100853 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国临床药理学与治疗学》2004年第4期382-385,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家 8 63计划重大专项 (№ 2 0 0 2AA2Z3 13 7)

摘　　要：目的 :研究新型抗高血压药物盐酸埃他卡林(Ipt)对血管内皮细胞分泌功能的影响。方法 :采用灌流消化法分离小牛主动脉内皮细胞 (BAEC) ,观察Ipt对BAEC分泌内皮素 1(ET 1)、前列环素 (PGI2 )和一氧化氮 (NO)的影响 ,同时观察Ipt对培养的BAEC胞浆游离Ca2 + 浓度的影响。结果 :在Ipt浓度为 10 -6mol·L-1及以上时 ,能够剂量依赖性地抑制培养的BAEC合成分泌ET 1,并在Ipt 10 -5mol·L-1及以上时促进NO的合成分泌 ,同时在Ipt浓度为10 -4mol·L-1及以上时 ,显著地增高BAEC胞浆游离Ca2 + 浓度。结论 :Ipt通过抑制内皮细胞合成分泌ET 1和促进NO的合成分泌 ,从而使ET和NO的平衡状态得到改善 ;尚能增加内皮细胞 [Ca2 + ]i,有利于内皮细胞合成NO增加 ,从而增强内皮介导的舒血管效应。AIM : To study the effects of the novel antihypertensive drug iptakalim hydrochloride (Ipt) on the secretion function of blood vessel endothelial cells. METHODS : Bovine aortic endothelial cells (BAEC) were obtained by using digestion technique. Effects of Ipt on the endothelin-1 (ET-1), prostacyclin (PGI 2) and nitric oxide (NO) secretion by BAEC were studied and effects of Ipt on the intracellular calcium concentration in BAEC were examined by miocrofluorometry of Fura-2/AM loaded cells. RESULTS : Ipt at 10 -6 mol·L -1 or more could inhibit cultured bovine aortic endothelial cells from producing and releasing endothelin-1 in a concentration-dependent manner, together with an increase in NO production. Moreover, Ipt at 10 -4 mol·L -1 or more induced a rapid elevation of intracellular calcium concentration in BAEC. CONCLUSION : Ipt can improve the balance between the release of relaxing and contracting factors from the endothelium by inhibiting ET-1 production and enhancing NO production in BAEC. The elevation effect of i by Ipt is essential for the cytoplasm synthesis of NO, and the effect may favorably enhance endothelium-mediated dilation.

关 键 词：盐酸埃他卡林 血管内皮细胞 内皮素-1 前列环素 一氧化氮 

分 类 号：R971[医药卫生—药品] R966[医药卫生—药学]