氯沙坦、福辛普利对高血压大鼠心肌纤维化、血管紧张素Ⅱ及左室重构的影响

Effects of Lorsartan, Fosinopril on myocardial fibrosis, angiotensin Ⅱ and cardiac remolding in hypertensive rats

目的 评价氯沙坦、福辛普利对自发性高血压大鼠 (SHR)心肌纤维化、左室重构及血浆和心肌组织中血管紧张素Ⅱ的效应。方法 :16周龄SHR随机分为 3组 ,即氯沙坦治疗组 (SHR L组 )、福辛普利治疗组 (SHR F组 )、空白对照组 (SHR C组 ) ,每组各 10只。分别采用病理检查及放射免疫测定方法对治疗 8周、16周的SHR心肌胶原容积分数 (CVF)和心肌血管周围胶原面积 (PVCA)、血浆和组织中血管紧张素Ⅱ进行检测。结果 :在治疗 8周、16周后 ,两治疗组的收缩压较对照组均有明显下降 ;治疗组组间比较差异无显著性 (P >0 .0 5 ) ;心脏重量 (HW )、心脏重量指数(HWI)、左室重量 (LVW)、左室重量指数 (LVMI)均有显著性改善 ,且治疗 16周后SHR F组较SHR L组LVMI显著性降低 (P <0 .0 5 )。两治疗组CVF和PVCA与对照组比较明显下降 (P <0 .0 1)。治疗 16周后SHR F组CVF较SHR L组下降更明显。SHR L组血浆及心肌组织中AngⅡ显著增加 ,而SHR F组心肌组织AngⅡ显著下降 ,但对血浆AngⅡ无明显影响。结论 :氯沙坦、福辛普利均能有效逆转心脏肥厚及抗心肌纤维化 ,以福辛普利作用显著。其作用机制可能与拮抗心肌组织中肾素 血管紧张素 醛固酮系统 (RAS)效应有关。

Objective: To investigate effects of lorsartan, fosinopril on myocardial fibrosis, angiotensin Ⅱ and cardiac remolding in the spontaneously hypertensive rats (SHR). Methods: 16 week old SHRs were divided randomly into 3 groups: SHR L (treated with lorsartan), SHR F (treated with fosinopril) and SHR C (untreated), each group consisting of 10 rats. After 8 weeks' and 16 weeks' therapeutic period, collagen volume fraction (CVF), perivascular circuferential area (PVCA), plasma and myocardium angiotensin Ⅱ concentrations were examined by pathological examination with computed processing and radioimmunoassay respectively. Results: (1) Compared with SHR C after 8 weeks' and 16 weeks' therapeutic period, the systolic blood pressure (SBP) was decreased similarly in both treatment groups. Heart and left ventricular weights, heart weight and eft ventricular mass indexes were lower significantly in both treatment groups than in SHR C. Left ventricular mass index was reduced to a lower extent in SHR F group than in SHR L group after 16 weeks. (2) Compared with SHR C, CVF, PVCA after 8 weeks and 16 weeks were reduced significantly in SHR F and SHR L. Meanwhile, CVF after 16 weeks in SHR F than in SHR L. (3) Compared with SHR C after both therapeutic periods, plasma and myocardium angiotensin Ⅱ concentrations were increased Significantly in SHR L, but plasma angiotensin Ⅱ concentrations were not altered significantly in SHR F. However, myocardium angiotensin Ⅱ concentrations were reduced significantly in SHR F after 8 weeks and 16 weeks in SHR F. Conclusion: Lorsartan, fosinopril inhibit myocardial fibrosis and reverse heart hypertrophy. Fosinopril may be more effective in these above effects than Lorsartan. The mechanism of the both drug's cardioprotective effects was related to inhibition of myocardium rennin angiotension aldsteron system.