Zhu X Q, Hong H S, Lin X H, Chen L L, Li Y H
Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Braz J Med Biol Res. 2014 Aug;47(8):646-54. doi: 10.1590/1414-431x20143474. Epub 2014 Jul 11.
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.
异丙肾上腺素（ISO）诱导的慢性心力衰竭（CHF）所涉及的生理机制尚未完全明确。在本研究中，我们调查了ISO诱导的CHF大鼠心脏醛固酮及其合成酶的局部变化，并评估了重组人脑钠肽（rhBNP）治疗的效果。将Sprague-Dawley大鼠分为4组。50只大鼠接受皮下注射ISO以诱导CHF，对照组（n = 10）注射等量生理盐水。建立大鼠模型后，9只CHF大鼠未接受进一步治疗，低剂量组（n = 8）大鼠每天接受22.5μg/kg rhBNP，高剂量组（n = 8）大鼠每天接受45μg/kg rhBNP，持续1个月。通过超声心动图和血流动力学分析评估心功能。测定胶原容积分数（CVF）。采用放射免疫分析法测定血浆和心肌醛固酮浓度。通过定量实时PCR检测心肌醛固酮合成酶（CYP11B2）。CHF组的心功能明显低于对照组（P < 0.01），而CVF、血浆和心肌醛固酮以及CYP11B2转录水平明显高于对照组（P < 0.05）。低剂量和高剂量的rhBNP均显著改善了血流动力学（P < 0.01）和心功能（P < 0.05），并降低了CVF、血浆和心肌醛固酮以及CYP11B2转录水平（P < 0.05）。rhBNP剂量组之间无显著差异（P > 0.05）。在ISO诱导的CHF大鼠中检测到心脏醛固酮升高和醛固酮合成酶表达上调。rhBNP给药可能通过下调CYP11B2转录和减少心肌醛固酮合成来改善血流动力学和心室重构，并减轻心肌纤维化。
