Combined Effects of Low-Dose Oral Spironolactone and Captopril Therapy in a Rat Model of Spontaneous Hypertension and Heart Failure

J Cardiovasc Pharmacol. 2003 Jun;41(6):830-7. doi: 10.1097/00005344-200306000-00002.


The effects of low-dose oral spironolactone (SPIRO) in a rat model of hypertensive heart failure (spontaneously hypertensive heart failure rat) were compared with its effects when combined with captopril (CAP). Twenty-six spontaneously rats with hypertensive heart failure were treated with either placebo (CON), SPIRO (20 mg/kg/d by mouth), CAP (100 mg/kg/d by mouth), or both SPIRO and CAP for 12 weeks. This dose of oral SPIRO did not affect blood pressure, left ventricular end-diastolic diameter, left ventricular ejection fraction, plasma atrial natriuretic peptide concentration, or cardiac fibrosis; however, in combination with CAP, it exerted a significant depressor effect after 12 weeks of treatment that was accompanied by increased urine output and decreased urinary protein excretion. These effects were significantly greater than those with CAP treatment alone. A significant increase in plasma aldosterone level was observed only in CON (174 +/- 21%). These data suggest that the addition of low-dose SPIRO to angiotensin I-converting enzyme inhibitor treatment may prevent progression into end-stage congestive heart failure through synergistic effects on diuresis and renoprotection.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Aldosterone / blood
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Atrial Natriuretic Factor / blood
  • Blood Pressure / drug effects
  • Captopril / administration & dosage
  • Captopril / pharmacology*
  • Diuresis / drug effects
  • Drug Therapy, Combination
  • Fibrosis
  • Heart Failure / drug therapy*
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / drug effects
  • Heart Ventricles / pathology
  • Hypertension / drug therapy*
  • Hypertrophy
  • Male
  • Mineralocorticoid Receptor Antagonists / administration & dosage
  • Mineralocorticoid Receptor Antagonists / pharmacology*
  • Myocardium / pathology
  • Organ Size / drug effects
  • Rats
  • Rats, Inbred SHR
  • Spironolactone / administration & dosage
  • Spironolactone / pharmacology*
  • Time Factors
  • Ultrasonography


  • Angiotensin-Converting Enzyme Inhibitors
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Aldosterone
  • Atrial Natriuretic Factor
  • Captopril