缬沙坦、螺内酯及其联用对逆转自发性高血压大鼠心肌重塑的影响

Effects of valsartan and/or spironolactone on myocardial remodeling in the spontaneous hypertensive rats

目的 在受体水平阻断肾素 血管紧张素 醛固酮系统 ,比较缬沙坦、螺内酯以及二者联用对逆转自发性高血压大鼠 (SHRs)心肌重塑的作用 ,来探讨高血压性心肌重塑的可能机制。方法 12周龄SHRs 32只 ,随机分成 4组 ,即SHR对照组、缬沙坦组、螺内酯组、二者联用 ,每组 8只 ;另设WKY大鼠(8只 ,周龄及体重同SHRs)为正常对照。Tail cuff法测血压 ,每周一次。 4个月后处死大鼠 ,测定左心室重量指数 (LVMI)、心肌胶原含量 (MCC)及心肌胶原容积分数 (CVF)。放免法检测血浆及心肌醛固酮水平。结果 与SHR对照组比较 ,螺内酯组收缩压稍降低 (P >0 0 5 ) ,缬沙坦组收缩压降低 (P <0 0 5 ) ,联用组收缩压显著降低 (P <0 0 1) ;三组的LVMI均降低 (P <0 0 5 ) ;三组的心肌胶原含量 (MCC)和心肌胶原容积分数 (CVF)下降 (P <0 0 5 ) ,其中 ,联用组效果优于缬沙坦组和螺内酯组 ;缬沙坦组的血浆、心肌醛固酮水平稍下降 (P >0 0 5 ) ,螺内酯组的血浆醛固酮水平显著升高 (P <0 0 5 )、心肌醛固酮水平显著下降 (P <0 0 1) ;联用组的心肌醛固酮水平显著下降 (P <0 0 1) ,与WKY鼠组接近。结论 首次证实在SHRs中长期使用血管紧张素 1型受体 (AT1)拮抗剂可导致血浆及心肌醛固酮逃逸。尽管螺内酯单独使用有效 ,但缬沙坦?

Objects To observe the inhibitory effects on the renin-angiotensin-aldosterone system by using valsartan and/or spironolactone in the spontaneous hyepertensive rats (SHRs). Methods Thirty-two SHRs were randomly divided into 4 groups:SHR-P(Placebo), SHR-S(treated with spironolactone), SHR-V(treated with valsartan) and SHR-C(treated with combination of spironolactone and valsartan). Systolic blood pressure(SBP), left ventricular mass index(LVMI), myocardial collagen contents(MCC), collagen volume fraction(CVF), plasma and myocardial aldosterone concentration were measured.Results Compared with SHR-P, SBP was decreased in SHR-V(P<0.05) and SHR-C(P<0.01), respectively. LVMI, MCC and CVF were decreased similarly in the three treatment groups (P<0.05). Compared with SHR-P, plasma and myocardial aldosterone concentration in SHR-V were decreased (P>0.05); plasma aldosterone concentration in SHR-S was significantly increased (P<0.05),while myocardial aldostereone concentration was significantly decreased (P<0.01).Myocardium aldosterone concentration in SHR-C was decreased (P<0.01). Conclusion This study shows long-term administration of Angiotensin Ⅱ type 1 receptors (AT1) antagonist can cause plasma and myocardial aldosterone escape in hypertensive cardiovascular tissue.The combining use of valsartan and spironolactone can normalize myocardial aldosterone and ventricular remodeling.