The physiological mechanisms involved in
isoproterenol (ISO)-induced chronic
heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac
aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human
brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO
injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis.
Collagen volume fraction (CVF) was determined. Plasma and myocardial
aldosterone concentrations were determined using radioimmunoassay. Myocardial
aldosterone synthase (
CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial
aldosterone, and
CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial
aldosterone, and
CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac
aldosterone and upregulation of
aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and
ventricular remodeling and reduced myocardial
fibrosis, possibly by downregulating
CYP11B2 transcription and reducing myocardial
aldosterone synthesis.