Luo Jinghong, Chen Xuanlan, Luo Chufan, Lu Guihua, Peng Longyun, Gao Xiuren, Zuo Zhiyi
Department of Cardiology, First Affiliated Hospital, Zhong-Shan University, Guangzhou, China.
Department of Geriatrics, Huizhou Municipal Central Hospital, Guangdong, China.
Cardiovasc Ther. 2017 Apr;35(2). doi: 10.1111/1755-5922.12246.
Our previous study indicates that hydrochlorothiazide inhibits transforming growth factor (TGF)-β/Smad signaling pathway, improves cardiac function and reduces fibrosis. We determined whether these effects were common among the diuretics and whether angiotensin II receptor type 1 (AT1) signaling pathway played a role in these effects.
Heart failure was produced by ligating the left anterior descending coronary artery in adult male Sprague Dawley rats. Two weeks after the ligation, 70 rats were randomly divided into five groups: sham-operated group, control group, valsartan group (80 mg/kg/d), hydrochlorothiazide group (12.5 mg/kg/d) and furosemide group (20 mg/kg/d). In addition, neonatal rat ventricular fibroblasts were treated with angiotensin II.
After eight-week drug treatment, hydrochlorothiazide group and valsartan group but not furosemide group had improved cardiac function (ejection fraction was 49.4±2.1%, 49.5±1.8% and 39.9±1.9%, respectively, compared with 40.1±2.2% in control group), reduced cardiac interstitial fibrosis and collagen volume fraction (9.7±1.2%, 10.0±1.3% and 14.1±0.8%, respectively, compared with 15.9±1.1% in control group), and decreased expression of AT1, TGF-β and Smad2 in the cardiac tissues. In addition, hydrochlorothiazide reduced plasma angiotensin II and aldosterone levels. Furthermore, hydrochlorothiazide inhibited angiotensin II-induced TGF-β1 and Smad2 protein expression in the neonatal rat ventricular fibroblasts.
Our study indicates that the cardiac function and remodeling improvement after ischemic heart failure may not be common among the diuretics. Hydrochlorothiazide may reduce the left ventricular wall stress and angiotensin II signaling pathway to provide these beneficial effects.
我们之前的研究表明，氢氯噻嗪可抑制转化生长因子（TGF）-β/Smad信号通路，改善心脏功能并减少纤维化。我们确定这些作用在利尿剂中是否常见，以及1型血管紧张素II受体（AT1）信号通路在这些作用中是否发挥作用。
通过结扎成年雄性Sprague Dawley大鼠的左冠状动脉前降支制备心力衰竭模型。结扎两周后，将70只大鼠随机分为五组：假手术组、对照组、缬沙坦组（80毫克/千克/天）、氢氯噻嗪组（12.5毫克/千克/天）和呋塞米组（20毫克/千克/天）。此外，用血管紧张素II处理新生大鼠心室成纤维细胞。
经过八周的药物治疗后，氢氯噻嗪组和缬沙坦组而非呋塞米组的心脏功能得到改善（射血分数分别为49.4±2.1%、49.5±1.8%和39.9±1.9%，而对照组为40.1±2.2%），心脏间质纤维化和胶原容积分数降低（分别为9.7±1.2%、10.0±1.3%和14.1±0.8%，而对照组为15.9±1.1%），并且心脏组织中AT1、TGF-β和Smad2的表达减少。此外，氢氯噻嗪降低了血浆血管紧张素II和醛固酮水平。此外，氢氯噻嗪抑制血管紧张素II诱导的新生大鼠心室成纤维细胞中TGF-β1和Smad2蛋白表达。
我们的研究表明，缺血性心力衰竭后心脏功能和重塑的改善在利尿剂中可能并不常见。氢氯噻嗪可能通过降低左心室壁应力和血管紧张素II信号通路来产生这些有益作用。
