盐酸埃他卡林对内皮素1诱导人离体肺动脉收缩的拮抗作用  

Effects of iptakalim on endothelin-1-induced vasoconstriction of isolated human pulmonary artery

作　　者：张宁[1] 张石江[1] 朱煜明[2] 解卫平[2] 王虹[2] 

机构地区：[1]南京医科大学第一附属医院心胸外科,210029 [2]南京医科大学第一附属医院呼吸病科,210029

出　　处：《江苏医药》2007年第5期436-438,共3页Jiangsu Medical Journal

基　　金：江苏省自然科学基金资助项目(BK2006246)

摘　　要：目的研究新型ATP敏感性钾通道(KATP)开放剂埃他卡林(IPT)对内皮素1(ET-1)诱导的人离体肺动脉收缩的影响及其机制。方法建立ET-1诱导人离体肺动脉收缩的量效反应曲线和时效反应曲线,以吡那地尔(PIN)为阳性对照,研究IPT不同浓度累积给药的舒张血管效应。结果在0·05～50nmol/L浓度范围内,ET-1呈浓度依赖性地引起肺动脉收缩。其半数有效浓度±95%可信区间(EC50±L95)为(10·19±1·26)nmol/L,曲线斜率±标准差(b±sb)为0·905±0·186,相关系数r=0·91。在10-13～10-3nmol/L浓度累积给药时,IPT呈浓度依赖性地拮抗ET-1诱导的肺动脉环收缩。其半数抑制浓度IC50为27·11nmol/L。结论IPT可以显著拮抗ET-1诱导的肺动脉收缩,其机制在于开放肺动脉平滑肌细胞上的KATP通道。IPT可以有效舒张人肺血管。Objective To investigate the vasodilative effects and mechanism of iptakalim （IPT）, a novel KATe channel opener, on the vasoconstriction of isolated human pulmonary artery induced by endothelin-1（ET-1）. Methods The effects of IPT administered by cumulative method on vasoconstriction mediated by ET-1 were studied with the rings of pulmonary artery isolated from the lungs, which were collected from thirty-eight patients with lung tumor underwent lobectomy. Vascular tensions were recorded under cumulative concentration of normal saline, IPT and pinacidil （PIN）. Results At the concentrations of 0. 05-50 nmol/L, ET-1 induced a significant increase of vascular tension in a concentration-dependent manner（EC50 ±95,10. 19 ± 1.26 nmol/L, r= 0. 91）. IPT at the concentrations of 10^-13 -10^-3 nmol/L, antagonized vasoconstriction induced by ET-1 in a concentra- tion-dependent manner （IC50,27. 11 nmol/L）. Conclusion IPT can significantly antagonize the vasoconstriction induced by ET-1 through activating KATe channel in the artery. IPT may dilate effectively human pulmonary artery.

关 键 词：ATP敏感性钾通道 盐酸埃他卡林 肺动脉 内皮素1 肺动脉高压 

分 类 号：R563[医药卫生—呼吸系统]