Hydrochlorothiazide modulates ischemic heart failure-induced cardiac remodeling via inhibiting angiotensin II type 1 receptor pathway in rats
| Autor: | Xiuren Gao, Guihua Lu, Xuanlan Chen, Longyun Peng, Chufan Luo, Zhiyi Zuo, Jinghong Luo |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
Cardiac function curve medicine.medical_specialty Heart Ventricles Angiotensin II Signaling Pathway Smad2 Protein 030204 cardiovascular system & hematology Receptor Angiotensin Type 1 Ventricular Function Left Rats Sprague-Dawley Transforming Growth Factor beta1 03 medical and health sciences 0302 clinical medicine Hydrochlorothiazide Furosemide Internal medicine medicine Animals Pharmacology (medical) Diuretics Aldosterone Cells Cultured Heart Failure Pharmacology Angiotensin II receptor type 1 Ejection fraction Ventricular Remodeling business.industry Angiotensin II Stroke Volume Recovery of Function General Medicine Fibroblasts medicine.disease Fibrosis Disease Models Animal Endocrinology Animals Newborn Valsartan Heart failure Cardiology and Cardiovascular Medicine business Angiotensin II Type 1 Receptor Blockers 030217 neurology & neurosurgery Signal Transduction medicine.drug |
| Zdroj: | Cardiovascular Therapeutics. 35:e12246 |
| ISSN: | 1755-5914 |
| Popis: | Aims 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. Methods 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/day), hydrochlorothiazide group (12.5 mg/kg/day) and furosemide group (20 mg/kg/day). In addition, neonatal rat ventricular fibroblasts were treated with angiotensin II. Results 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. Conclusions 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. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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