In:
Journal of Cardiovascular Pharmacology, Ovid Technologies (Wolters Kluwer Health), Vol. 71, No. 4 ( 2018-04), p. 205-214
Abstract:
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 ZSF 1 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 ZSF 1 rats aged 20 to 44 weeks. Untreated ZSF 1 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.
Type of Medium:
Online Resource
ISSN:
0160-2446
DOI:
10.1097/FJC.0000000000000561
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2018
detail.hit.zdb_id:
2049700-3
SSG:
15,3
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