奥美沙坦抑制低渗液诱导的豚鼠心房肌细胞I_(Ks)电流增加和动作电位时程缩短  

Olmesartan attenuates the hyposmosis-induced enhancement of I_(Ks) current and the shortening of action potential duration in guinea-pig atrial myocytes

作　　者：高洁[1] 盛婴[2] 叶莎[1] 刘传镐[3] 赵进[4] 

机构地区：[1]西安交通大学第二附属医院干部二病区,西安710004 [2]西安交通大学第一附属医院干五病区 [3]西安交通大学医学部药理学系 [4]西安交通大学医学部机能教学中心

出　　处：《山西医科大学学报》2015年第4期283-288,共6页Journal of Shanxi Medical University

基　　金：陕西省科学技术研究发展计划基金资助项目(2011k4-07);西安交通大学第二附属医院科研基金/人才培养专项基金资助项目(2003-YL-28)

摘　　要：目的研究选择性AT1受体阻滞剂(ARB)奥美沙坦对牵拉心房肌细胞诱导的IKs电流增加和动作电位时程(APD)缩短的影响,探讨ARB防治房颤(AF)的可能机制。方法采用低渗液(Hypo-S,渗透压降低26%)作用于豚鼠心房肌细胞以模拟细胞牵张,然后利用膜片钳技术记录心房肌细胞IKs电流和APD。结果 1μmol/L和7μmol/L奥美沙坦可降低由Hypo-S诱导的豚鼠心房肌细胞IKs增加和动作电位复极90%时程(APD90)缩短,但不影响基础IKs电流。Hypo-S可使IKs电流增加105.60%,而Hypo-S+1μmol/L和Hypo-S+7μmol//L奥美沙坦仅分别使IKs电流增加70.64%和68.22%(与Hypo-S比较,均P<0.05)。同时,Hypo-S使APD90缩短20.22%,而Hypo-S+1μmol/L奥美沙坦和Hypo-S+7μmol/L奥美沙坦分别使APD90缩短11.89%和11.56%(与Hypo-S比较,均P<0.01)。结论奥美沙坦对牵张心房肌细胞诱导的电生理变化与阻断AT1受体有关。由于房颤时常伴有心房肌细胞扩张和有效不应期增加,因而奥美沙坦的作用有益于心房纤颤治疗。Objective To explore the effects of olmesartan,a selective AT1 R blocker（ ARB）,on the enhancement of IKsand the shortening of action potential duration（ APD） induced by stretching atrial myocytes,and to explain the possible mechanism underlying the prevention of atrial fibrillation（ AF） by ARB.Methods Hyposmotic solution（ Hypo-S,26% reduction in osmolarity） was used to stretch guinea-pig atrial myocytes.IKsand APD were recorded using the whole-cell patch-clamp technique.Results Olmesartan of1-7 μmol / L attenuated both the increase of IKswithout affecting baseline currents and the shortening of APD90 induced by Hypo-S.Hypo-S increased the IKsby 105.60%,whereas Hypo-S ＋ 1 μmol / L olmesartan and Hypo-S ＋ 7 μmol / L olmesartan increased the IKsby70.64%（ P 〈0.05 vs Hypo-S） and 68.22%（ P 〈0.05 vs Hypo-S）,respectively.Meanwhile,Hypo-S shortened the APD90by20.22%,whereas Hypo-S ＋ 1 μmol / L olmesartan and Hypo-S ＋ 7 μmol / L olmesartan shortened the APD90 by 11.89% and 11.56%（ P〈 0.01 vs Hypo-S） respectively.Conclusion These results suggest that the actions of olmesartan on electrical changes induced by stretching atrial myocytes are associated with AT1 R blockade and may be beneficial to the treatment of AF which is accompanied by atrial dilation and increased effective refractory period.

关 键 词：1型血管紧张素Ⅱ受体 奥美沙坦 心房肌细胞 IKS 动作电位 

分 类 号：R96[医药卫生—药理学]