Department of Cardiology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
Eur J Pharmacol. 2011 Sep 30;667(1-3):314-21. doi: 10.1016/j.ejphar.2011.06.012. Epub 2011 Jun 17.
Heart failure is a major cause of morbidity and mortality worldwide. Diuretics are regarded as the first-line treatment for patients with heart failure because they provide symptomatic relief. However, the specific benefits of diuretics and their effects on heart failure survival remain unclear. This study was designed to investigate the potential of hydrochlorothiazide to improve cardiac remodeling compared with spironolactone. Heart failure was produced by ligation of the left anterior descending coronary artery in male Sprague-Dawley rats. Two weeks after coronary artery ligation, 55 rats were randomly divided into four groups: sham-operated group (n=10), control group (n=15), hydrochlorothiazide group (12.5 mg/kg/day, n=15) and spironolactone group (20 mg/kg/day, n=15). Cardiac function was assessed by echocardiography and Millar catheter after treatment with drugs for 8 weeks. Compared with the control group, ejection fraction and left ventricular end-systolic pressure were significantly improved in the hydrochlorothiazide and spironolactone treatment groups (P<0.05). In addition, hydrochlorothiazide and spironolactone reduced collagen volume fraction and proinflammatory cytokine levels. Moreover, gene and protein expression of TGF-β1, Smad2, Smad3 and Smad7 (P<0.05) were also reduced. Nevertheless, no significant differences were observed between the hydrochlorothiazide and spironolactone groups. These results suggest that hydrochlorothiazide improves cardiac remodeling as effectively as spironolactone by reducing proinflammatory cytokine levels and inhibiting the TGF-β signaling pathway in post-myocardial infarction congestive heart failure. Moreover, the effects of the drugs on the TGF-β signaling pathway are likely to result from inhibited TGF-β and R-Smads expression rather than increased Inhibitory-Smad7 expression.
心力衰竭是全球发病率和死亡率的主要原因。利尿剂被认为是心力衰竭患者的一线治疗药物，因为它们可以提供症状缓解。然而，利尿剂的具体益处及其对心力衰竭生存的影响仍不清楚。本研究旨在探讨氢氯噻嗪与螺内酯相比改善心脏重构的潜力。雄性 Sprague-Dawley 大鼠通过结扎左前降支冠状动脉来产生心力衰竭。冠状动脉结扎后 2 周，将 55 只大鼠随机分为四组：假手术组（n=10）、对照组（n=15）、氢氯噻嗪组（12.5mg/kg/天，n=15）和螺内酯组（20mg/kg/天，n=15）。用药物治疗 8 周后，通过超声心动图和 Millar 导管评估心功能。与对照组相比，氢氯噻嗪和螺内酯治疗组的射血分数和左心室收缩末期压明显改善（P<0.05）。此外，氢氯噻嗪和螺内酯降低了胶原容积分数和促炎细胞因子水平。此外，TGF-β1、Smad2、Smad3 和 Smad7 的基因和蛋白表达也降低（P<0.05）。然而，氢氯噻嗪组和螺内酯组之间没有观察到显著差异。这些结果表明，氢氯噻嗪通过降低促炎细胞因子水平和抑制 TGF-β 信号通路，与螺内酯一样有效地改善心肌梗死后充血性心力衰竭的心脏重构。此外，药物对 TGF-β 信号通路的作用可能是由于抑制 TGF-β 和 R-Smads 表达，而不是增加抑制性 Smad7 表达所致。
