盐酸埃他卡林对高血压心脏重构的作用

Effects of iptakalim hydrochloride on hypertensive cardiac remodeling

目的 在自发性高血压大鼠 (spontaneouslyhyperten siverat,SHR)和脑卒中易感型自发性高血压大鼠 (stroke pronespontaneouslyhypertensiverat,SHRsp)上 ,评价盐酸埃他卡林 (iptakalimhydrochloride ,Ipt)对高血压心脏重构的实验治疗学作用。方法 SHR于第 12周龄进入实验 ,赖诺普利 (lisinopril,Lis) 12mg·kg-1,Ipt 3mg·kg-1灌胃每天 1次 ,连灌 4wk ;SHRsp于第 11周龄进入实验 ,实验设Ipt0 2 5、1和 4mg·kg-13个剂量组及溶剂对照组 ,灌胃给药每天 1次 ,持续给药 12wk ,观察药物对高血压心脏重构的影响。结果 实验期 4wk内 ,SHR对照组血压和心率进行性增高。Ipt能有效控制SHR的血压 ,降压效果确切 ,且可抑制SHR心率加快的趋势 ,但对SHR高血压心脏重构无明显作用。相同实验条件下 ,Lis也能有效控制SHR的血压 ,降压效果确切 ,对心率无明显影响 ;Lis治疗可减轻SHR高血压心脏重构。实验期 12wk内 ,SHRsp溶剂对照组血压持续性进行性增高。Ipt 3个剂量组均能降低SHRsp血压 ,Ipt 4mg·kg-1组在给药后第 4周开始出现心率减低。Ipt 3个剂量组的左心室和室间隔 (LV +S)重量及其与体重的比值[(LV +S) /BW ]低于溶剂对照组。 4组动物之间的右室重量(RV)均无差异。结论 Ipt能有效地控制SHR和SHRsp的血压 。

AIM To study the experimental therapeutic effects of iptakalim hydrochloride(Ipt) on hypertensive cardiac remodeling in spontaneously hypertensive rats(SHR) and stroke prone spontaneously hypertensive rats(SHRsp). METHODS SHR at the age of 12 week old were treated ig with lisinopril 12 mg·kg -1 ·d -1 or Ipt 3 mg·kg -1 ·d -1 , once a day for 30 days. Age matched Wistar rats were used as normal control. 10 week old SHRsp were treated ig with Ipt 0 25,1 0 and 4 0 mg·kg -1 , once a day for 12 weeks. Age matched Wistar rats were used as normal control. After killing animals, the effects of Ipt on hypertensive cardiac remodeling were investigated. RESULTS During the 4 week experimental period, the systolic blood pressure(SBP) and heart rates(HR) of the untreated SHR were increased progressively. Ipt 3 mg·kg -1 ·d -1 could decrease SBP effectively and inhibit the increasing tendency of HR. Ipt had no effects on hypertensive cardiac remodeling in SHR. Under the same experimental conditions, lisinopril 12 mg·kg -1 ·d -1 could decrease SBP effe-ctively and had no effects on HR. The hypertensive cardiac remodeling could be alleviated by lisinopril. During the 12 week experimental period, the SBP of the untreated SHRsp were increased progressively. Ipt 0 25,1 0 and 4 0 mg·kg -1 could decrease the SBP of SHRsp effectively. Ipt at the doses of 0 25 and 1 0 mg·kg -1 had no effects on heart rates. But in the 4th week after administration of Ipt 4 0 mg·kg -1 , significant decrease in heart rates was observed. Compared with Wistar rats, the weight of left ventricle and septum(LV+S) and the ratio of LV+S to body weight(LV+S/BW) in untreated SHRsp were elevated significantly. Ipt 0 25, 1 0 and 4 0 mg·kg -1 ·d -1 could decrease LV+S and LV+S/BW significantly. CONCLUSION Ipt could decrease SBP of SHR and SHRsp effectively. The effects of Ipt on hypertensive cardiac remodeling were related with the experimental therapeutic period. After having been treated with Ipt for 4 weeks, the hypertensive cardiac remodeling could not be reversed. But after having been treated with Ipt for 12 weeks, the hypertensive cardiac remodeling could be reversed significantly.