Heart failure with preserved ejection fraction (HFpEF), a prevalent form of
heart failure, is frequently accompanied by the
metabolic syndrome and
kidney disease. Because current treatment options of HFpEF are limited, evaluation of
therapies in experimental models of HFpEF with the
metabolic syndrome and
kidney disease is needed. In this study, we evaluated the effects of
captopril,
furosemide, and their combination in aged, obese ZSF1 rats, an animal model of HFpEF with the
metabolic syndrome and
chronic kidney disease as comorbidities.
Captopril (100 mg/kg),
furosemide (50 mg/kg), or their combination was administered orally to obese ZSF1 rats aged 20 to 44 weeks. Untreated ZSF1 rats served as controls. After 24 weeks of treatment,
captopril significantly lowered systemic blood pressure and attenuated HFpEF as evidenced by significantly reduced left ventricular end diastolic pressures (10.5 ± 1.4 vs. 4.9 ± 1.3 mm Hg in Control vs.
Captopril, respectively) and significantly lower left ventricular relaxation time constants (28.1 ± 2.9 vs. 18.3 ± 3.1 ms in Control vs.
Captopril, respectively). The
captopril-induced improvement in left ventricular function was associated with reduced
cardiac hypertrophy,
ischemia,
necrosis, and
vasculitis.
Captopril also increased renal blood flow and glomerular filtration rate, reduced renal vascular resistance and
proteinuria, and improved renal histology (ie, reduced renal
hypertrophy, glomerulosclerosis, and tubular
atrophy/dilation).
Furosemide alone provided little benefit; moreover,
furosemide did not augment the therapeutic benefits of
captopril. This study suggests that chronic administration of
captopril, but not
furosemide, could be beneficial in patients with HFpEF, particularly in those with comorbidities such as
obesity, diabetes, and
dyslipidemias.