Valsartan与benazepril联合应用对自发性高血压大鼠血压和左心室肥厚的影响

目的:评价血管紧张素转换酶抑制剂苯那普利钠和AT_1受体拮抗剂缬沙坦联合应用对自发性高血压大鼠(SHR)的降压疗效及其逆转心肌肥厚作用和对肾素-血管紧张素-醛固酮系统(RAAS)、内洋地黄素水平的影响.方法:24只14周龄雄性SHR随机分成空白对照组、Benazepril组、Valsartan组和Benazepril Valsartan组,另设WKY正常对照组.分别于药物干预前、药物干预后2、4、6、8周末测定大鼠SBP;于药物干预后8周末检测心肌组织和血浆肾素活性、血管紧张素Ⅱ浓度、心肌组织Na~ -K~ -ATP酶活性和内洋地黄素水平,并行心肌组织形态学检查.结果:药物干预各组SHR动脉收缩压(SBP)水平明显下降,尤以联合用药组SBP下降最显著;药物干预各组血浆和心肌组织肾素活性均明显升高;Benazepril组和Benazepril Valsartan组血浆和心肌组织Ang Ⅱ水平降低,而Valsartan组血浆和心肌组织Ang Ⅱ水平则明显升高;随SBP水平的降低,心肌组织Na~ -K~ -ATP酶活性明显升高,而内洋地黄素水平则明显下降;药物干预各组LVM/BW、TDM均明显减低,尤以联合用药组改变最为显著.结论:ACEI Benazepril和AT_1拮抗剂Valsartan均有明显的降低SHR的SBP作用,能明显逆转左室肥厚;联合用药效果最为显著,并能有效防止单一AT_1拮抗剂所致血浆和心肌组织Ang Ⅱ水平的升高的副作

Effect of combination of valsartan with benazepril on blood pressure and left ventricular hypertrophy in SHR

AIM: To evaluate the antihypertensive efficacy of angiotensin converting enzyme inhibitor (ACEI) benazepril in combination with AT1 receptor antagonist valsartan and their effect on left ventricular hypertrophy, renin angiotensin aldosterone system (RAAS) and endoxin in spontaneously hypertensive rat (SHR). METHODS: WKY control group (n = 6) and other 4 groups consisted of 24 SHR (14-week-old, male, n = 6): SHR control group, benazepril group, valsartan group, and combination drug therapy group. Systolic blood pressure (SBP) of SHR was measured at the beginning and at the end of 2, 4, 6, and 8 wk of drug intervention. Morphometric determination, renin activities, angiotensin II (Ang II), endoxin, and ATPase activity analysis were performed at the end of 8 week of drug intervention. RESULTS: SBP, ratio of left ventricular mass (LVM), body weight (BW) (LVM/BW), and transverse diameter of myocardial cell (TDM) of SHR were remarkably decreased after drug intervention, and this decrease was most remarkable in the combination drug therapy group. Renin activities of plasma and myocardium were remarkably increased in drug intervention groups. The levels of Ang II in plasma and myocardium were remarkably increased in valsartan group, decreased in benazepril group and combination drug therapy group. Na(+)-K(+)-ATPase activities in myocardium were remarkably increased and the level of endoxin in myocardium were remarkably decreased as SBP decreased after drug intervention. CONCLUSION: Both benazepril and valsartan can decrease SBP of SHR, and cause regression of ventricular hypertrophy. The efficacy of combination drug therapy group is most remarkable among all groups and avoids the side effects of induction of high Ang II levels in plasma and myocardium caused by long-term use of valsartan alone.