Effects of late-onset and long-term captopril and nifedipine treatment in aged spontaneously hypertensive rats: Echocardiographic studies

Hypertens Res. 2015 Nov;38(11):716-22. doi: 10.1038/hr.2015.68. Epub 2015 Jul 16.

Abstract

The purpose of the present study was to analyze the changes in blood pressure, left ventricular (LV) wall thickness and LV systolic function of aged spontaneously hypertensive rats (SHRs) either with or without antihypertensive therapy. Twenty-one SHRs aged 60.5±0.25 weeks were investigated over 22 weeks. They were divided into the following three groups (7 per group): untreated controls (CTRL), treatment with captopril (CAP, 60 mg kg(-1) daily) and treatment with captopril plus nifedipine (CAP+NIF, 60+10 mg kg(-1) daily). Systolic blood pressure (SBP) was regularly measured using the tail cuff method, and an echocardiogram was repeatedly obtained to examine the LV systolic and diastolic area, LV systolic fractional area change, cardiac output and LV myocardial wall thickness. Finally, heart catheterization was performed. While SBP remained stable in the CTRL animals over the experimental period, both of the antihypertensive treatments significantly reduced SBP by 20% in the treated animals (P<0.001). Echocardiography demonstrated that both the systolic and the diastolic LV function of the untreated SHRs deteriorated over time, whereas both types of antihypertensive treatments attenuated and delayed but did not completely prevent the decline in LV systolic function. Cardiac output, as determined by pulsed wave Doppler echocardiography, remained significantly higher in the treated animals than in CTRLs until week 20, but it then decreased. Heart catheterization showed a significant decrease in LV function, as reflected by the LV systolic pressure and contractility, in the CTRLs but not in treated animals. These findings clearly indicate that late-onset antihypertensive treatment with CAP or CAP+NIF is beneficial with respect to blood pressure reduction, LV hypertrophy attenuation and LV systolic function preservation.

MeSH terms

  • Animals
  • Antihypertensive Agents / administration & dosage*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / administration & dosage*
  • Captopril / administration & dosage*
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination
  • Echocardiography
  • Heart Failure / prevention & control
  • Hemodynamics / drug effects
  • Hypertension / diagnostic imaging
  • Hypertension / drug therapy*
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / prevention & control
  • Male
  • Nifedipine / administration & dosage*
  • Random Allocation
  • Rats, Inbred SHR
  • Systole / drug effects
  • Ventricular Dysfunction, Left / prevention & control
  • Ventricular Function, Left / drug effects

Substances

  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Captopril
  • Nifedipine