Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

Abstract

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.

In vivo effects of nitrosyl hydrogen on cardiac function and sarcoplasmic reticulum calcium pump (SERCA2a) in rats with heart failure after myocardial infarction

“…It is a type of disease characterized by systolic or (and) diastolic dysfunction (2), and is one of the important reasons for the decline in quality of life and even death. Recent studies have found that abnormal Ca 2+ circulation in cardiomyocytes is an important cause of decreased myocardial contractility in failing hearts (3)(4)(5)(6). However, in myocardial depolarization, mitochondria release Ca 2+ to the cytoplasm at a slower rate (3), which is also an important cause of the decrease in cytosolic Ca 2+ concentration.…”

Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy

“…Increased expression of aldosterone synthase (CYP11B2) in the hearts is related to fibrillation and fibrosis and in this study we have identified the increased expression of this protein in the hearts of CHF rats. Because of its additive anti‐aldosterone effects, torasemide treatment has been found to be effective in inhibiting the CYP11B2 expression and thereby preventing adverse cardiac remodeling in mice and interestingly, furosemide did not produce such effect .…”

Protective effects of recombinant human brain natriuretic peptide in perioperative period during open heart surgery

“…A related study also showed improvements in the hemodynamic parameters after 15 min of treatment ( 15 ). The natriuretic peptide could improve the heart rate through the comprehensive effect ( 16 ). The results of this study showed that postoperative LVEF were higher than preoperative in the two groups of patients, and the observation group was significantly higher than the control group after 7 days of treatment (P<0.05).…”