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

Acta Pharmacol Sin. 2000 Nov;21(11):1043-7.

Abstract

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.

MeSH terms

  • Angiotensin II / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Antihypertensive Agents / therapeutic use
  • Benzazepines / therapeutic use*
  • Blood Pressure / drug effects*
  • Drug Therapy, Combination
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Hypertrophy, Left Ventricular / drug therapy*
  • Male
  • Random Allocation
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Tetrazoles / therapeutic use*
  • Valine / analogs & derivatives
  • Valine / therapeutic use*
  • Valsartan

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Benzazepines
  • Tetrazoles
  • Angiotensin II
  • Valsartan
  • Valine
  • benazepril