Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model

被引：21

作者：

Huang, Chun-kai ^{[1
,2
]}

Chen, Bi-yi ^{[2
]}

Guo, Ang ^{[2
]}

Chen, Rong ^{[1
,2
]}

Zhu, Yan-qi ^{[1
,2
]}

Kutschke, William ^{[2
]}

Hong, Jiang ^{[1
]}

Song, Long-sheng ^{[2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Shanghai 200080, Peoples R China

[2] Univ Iowa, Dept Internal Med, Carver Coll Med, Div Cardiovasc Med, Iowa City, IA 52242 USA

[3] Dept Vet Affairs Med Ctr, Iowa City, IA 52242 USA

来源：

ACTA PHARMACOLOGICA SINICA | 2016年 / 37卷 / 04期

基金：

中国国家自然科学基金;

关键词：

sildenafil; PDE5; inhibitor; T-tubule; pressure overload; left ventricular remodeling; left heart failure; PHOSPHODIESTERASE; 5; INHIBITION; HUMAN FAILING CARDIOMYOCYTES; PRESERVED EJECTION FRACTION; CARDIAC-HYPERTROPHY; MYOCARDIAL-INFARCTION; REDUCED SYNCHRONY; CA2+ RELEASE; EXERCISE CAPACITY; CLINICAL STATUS; JUNCTOPHILIN-2;

D O I：

10.1038/aps.2016.13

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Aim: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has been shown to exert beneficial effects in heart failure. The purpose of this study was to test whether sildenafil suppressed transverse-tubule (T-tubule) remodeling in left ventricular (LV) failure and thereby providing the therapeutic benefits. Methods: A pressure overload-induced murine heart failure model was established in mice by thoracic aortic banding (TAB). One day after TAB, the mice received sildenafil (100 mg.kg(-1). d(-1), sc) or saline for 5 weeks. At the end of treatment, echocardiography was used to examine LV function. Then the intact hearts were dissected out and placed in Langendorff-perfusion chamber for in situ confocal imaging of T-tubule ultrastructure from epicardial myocytes. Results: TAB surgery resulted in heart failure accompanied by remarkable T-tubule remodeling. Sildenafil treatment significantly attenuated TAB-induced cardiac hypertrophy and congestive heart failure, improved LV contractile function, and preserved T-tubule integrity in LV cardiomyocytes. But sildenafil treatment did not significantly affect the chamber dilation. The integrity of LV T-tubule structure was correlated with cardiac hypertrophy (R-2= 0.74, P< 0.01) and global LV function (R-2= 0.47, P< 0.01). Conclusion: Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure.

引用

页码：473 / 482

页数：10

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