氯沙坦短期用药对高血压前期大鼠血压和心肌的后效应

The after-effect of short-term use of losartan on blood pressure and myocardium in prehypertension rats

目的观察氯沙坦短期用药对高血压前期大鼠血压和心肌的影响。方法 24只4周龄雄性自发性高血压大鼠均分3组,A组给生理盐水(NS),B组于4周龄时给20mg/kg氯沙坦,C组于12周龄时给20mg/kg氯沙坦;另取8只4周龄雄性京都种Wistar大鼠为D组,给NS作为正常对照。各组均每天1次灌胃给药持续4周,停药后随访观察至24周。各鼠分别于4、8、12、16、20及24周龄时采用尾套法测尾动脉收缩压(SBP);24周龄时断头取标本,称质量法测右心室质量/体质量比(RVW/BW)全心质量/体质量比(HW/BW)、左心室质量/体质量比(LVW/BW);苏木素-伊红(HE)染色法观察心肌组织形态学变化,测心肌细胞横断面面积;放射免疫法测血浆与心肌的血管紧张素Ⅱ(AngⅡ)和醛固酮(Aldo)水平。结果 SBP在8周龄时A、C组明显高于D组(P<0.05);B组明显低于A组(P<0.05),停药后,B组SBP上升缓慢,直至24周龄时均持续低于A组(P<0.05),也明显低于C组(P<0.05);C组16周龄时SBP明显低于A组(P<0.05),但仍明显高于D组,且在停药后迅速上升,至24周龄时与A组比较差异无统计学意义(P>0.05)。LVW/BW、HW/BW及心肌细胞面积,A组较D组明显增加(P<0.05),B、C组较A组明显减少或减小(P<0.05),B组较C组明显减少或减小(P<0.05)。心肌细胞横断面切片光镜下观察,A组较D组心肌细胞肥大、细胞间距增宽和间质纤维增生明显,B组与D组近似,C组介于B组与A组之间。血浆与心肌的AngⅡ和Aldo水平,A组较D组明显增高(P<0.05),B组较A、C组组明显降低(P<0.05)。结论氯沙坦短期用于高血压前期大鼠可获取降压和抗心室重构的后效应。

Objective To observe the influence of losartan on rats′blood pressure and myocardium.Methods To randomly divide 24 4-year-old spontaneously hypertensive male rats into 3groups.Group A is given normal saline（NS）;group B is given losartan 20mg/kg in 4-week-old;group C is given the same dose in 12-week-old;To take another 4-week-old male wistar rats to form group D,feed NS served as normal comparison.Each group was given NS or losartan one time each day through intragastric administration for 4weeks.Follow up 24 weeks after stopping the medicine.Rats＇ SBP were measured through tail cuff method respectively when at 4,8,12,16,20 and 24weeks＇ time.After 24 weeks,cut off the head to take the sample,the RVW/BW,HW/BW,LVW/BW were measured through weighing method.To observe the morphologic change of the cardiac muscles and measure the area of myocardium cell cross section through HE stain method.Radioimmunoassay was used to measure the AngⅡ and Aldo level of the blood plasma and myocardium.Results At the age of eight-week,the SBP of group A and C are higher than those of group D（P〈0.05）,group B significantly lower than group A.After stopping the medicine,SBP of group B is slowly increasing and still lower than group A（P〈0.05）as well as group C（P〈0.05）until the 24 th week.At the 16 th week,SBP of group C is significantly lower than that of group A（P〈0.05）but higher than group D,but quickly increases after stopping the medicine till the 24 th week and there is no significant difference between group A and C（P〈0.05）.About LVW/BW,HW/BW and the area of myocardium cell cross section,group A increased significantly in comparison with group D（P〈0.05）,group B and C decreased in comparison with group A（P〈0.05）,group B decreased significantly in comparison with group C（P〈0.05）.Through the observation of the area of myocardial cell cross section under the microscopy,group A increased significantly in comparison with group D about myocardial cell fattened and the gap between cells are widened,the fibers of mesenchyma proliferates.group B and D are similar,group C is between group B and A.The level of AngⅡ and Aldo in plasma and myocardium of group A increased significantly in comparison with group D（P〈0.05）,group B decreased significantly in comparison with group A and C（P〈0.05）.Conclusion To use losartan for a short time in treating rats with prehypertension can get the after-effect of reducing blood pressure and anti-ventricular-remodeling.