Effects of hydrochlorothiazide on cardiac remodeling in a rat model of myocardial infarction-induced congestive heart failure
| Autor: | Longyun Peng, Jinghong Luo, Hua-wei Sun, Xiuren Gao, Gang Dai |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Cardiac function curve medicine.medical_specialty Heart Ventricles Myocardial Infarction Volume overload Smad Proteins Rats Sprague-Dawley Electrolytes chemistry.chemical_compound Hydrochlorothiazide Transforming Growth Factor beta Internal medicine medicine Animals Myocardial infarction Ligation Heart Failure Pharmacology Ejection fraction Ventricular Remodeling business.industry Myocardium Hemodynamics medicine.disease Symptomatic relief Rats Disease Models Animal Gene Expression Regulation chemistry Heart failure Spironolactone Cardiology Cytokines Collagen business Signal Transduction medicine.drug |
| Zdroj: | European Journal of Pharmacology. 667:314-321 |
| ISSN: | 0014-2999 |
| Popis: | 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 (P0.05). 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 (P0.05) 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. |
| Databáze: | OpenAIRE |
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