Ke Y S, Cao H, Yang T
Department of Cardiology, Yijishan Hospital, Wannan Medical College, Wuhu 241001, China.
Acta Pharmacol Sin. 2000 Nov;21(11):1043-7.
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).
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.
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.
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.
评估血管紧张素转换酶抑制剂(ACEI)贝那普利与AT1受体拮抗剂缬沙坦联合应用的降压疗效及其对自发性高血压大鼠(SHR)左心室肥厚、肾素血管紧张素醛固酮系统(RAAS)和内毒素的影响。
WKY对照组(n = 6)和其他4组由24只SHR(14周龄,雄性,n = 6)组成:SHR对照组、贝那普利组、缬沙坦组和联合药物治疗组。在药物干预的第2、4、6和8周开始及结束时测量SHR的收缩压(SBP)。在药物干预8周结束时进行形态学测定、肾素活性、血管紧张素II(Ang II)、内毒素和ATP酶活性分析。
药物干预后,SHR的SBP、左心室质量(LVM)与体重(BW)之比(LVM/BW)以及心肌细胞横径(TDM)显著降低,联合药物治疗组降低最为显著。药物干预组血浆和心肌中的肾素活性显著升高。缬沙坦组血浆和心肌中的Ang II水平显著升高,贝那普利组和联合药物治疗组降低。药物干预后随着SBP降低,心肌中的Na(+)-K(+)-ATP酶活性显著升高,心肌中的内毒素水平显著降低。
贝那普利和缬沙坦均可降低SHR的SBP,并使心室肥厚消退。联合药物治疗组的疗效在所有组中最为显著,且避免了长期单独使用缬沙坦导致血浆和心肌中Ang II水平升高的副作用。