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

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 (P0.05). 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.异丙肾上腺素（isoproterenol, ISO）诱导慢性心力衰竭（chronic heart failure, CHF）的生理机制尚未完全阐明。本研究探究了ISO诱导CHF大鼠的心脏醛固酮（aldosterone）及其合酶的局部变化，并评估了重组人脑利钠肽（recombinant human brain natriuretic peptide, rhBNP）的干预效果。将斯普拉格-道利（Sprague-Dawley）大鼠分为4组：50只大鼠经皮下注射ISO以构建CHF模型，对照组（n=10）注射等体积生理盐水。模型构建完成后，9只CHF大鼠未接受额外干预；低剂量组（n=8）每日给予22.5 μg/kg的rhBNP，高剂量组（n=8）每日给予45 μg/kg的rhBNP，连续干预1个月。通过超声心动图与血流动力学分析评估心功能，测定胶原容积分数（collagen volume fraction, CVF）；采用放射免疫分析法检测血浆与心肌组织的醛固酮浓度；通过实时定量PCR（quantitative real-time PCR）检测心肌醛固酮合酶（CYP11B2）的表达水平。CHF组大鼠的心功能显著低于对照组（P0.05）。ISO诱导的CHF大鼠中可检测到心脏醛固酮水平升高及醛固酮合酶表达上调。给予rhBNP干预可改善血流动力学与心室重构，减轻心肌纤维化，其潜在机制可能为下调CYP11B2的转录水平，减少心肌醛固酮的合成。