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

Chun-kai Huang; Bi-yi Chen; Ang Guo; Rong Chen; Yan-qi Zhu; William Kutschke; Jiang Hong; Long-sheng Song

doi:10.1038/aps.2016.13

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

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

Chun-kai Huang, Bi-yi Chen, Ang Guo, Rong Chen, Yan-qi Zhu, William Kutschke, Jiang Hong and Long-sheng Song

Acta pharmacologica Sinica, Vol.37(4), pp.473-482

04/2016

DOI: 10.1038/aps.2016.13

PMCID: PMC4820805

PMID: 26972492

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Abstract

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. 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. 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). Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure.

Animals

Cardiomegaly - drug therapy

Cardiomegaly - pathology

Heart Failure - drug therapy

Heart Failure - pathology

Heart Failure - physiopathology

Male

Mice, Inbred C57BL

Phosphodiesterase 5 Inhibitors - therapeutic use

Sildenafil Citrate - therapeutic use

Ventricular Function, Left - drug effects

Ventricular Remodeling - drug effects

Details

Title: Subtitle: Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model
Creators: Chun-kai Huang - Shanghai Jiao Tong University
Bi-yi Chen - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Ang Guo - University of Iowa
Rong Chen - Shanghai Jiao Tong University
Yan-qi Zhu - University of Iowa
William Kutschke - University of Iowa
Jiang Hong - Shanghai Jiao Tong University
Long-sheng Song - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Acta pharmacologica Sinica, Vol.37(4), pp.473-482
DOI: 10.1038/aps.2016.13
PMID: 26972492
PMCID: PMC4820805
NLM abbreviation: Acta Pharmacol Sin
ISSN: 1671-4083
eISSN: 1745-7254
Grant note: R01 HL130346 / NHLBI NIH HHS R01 HL090905 / NHLBI NIH HHS
Language: English
Date published: 04/2016
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984288716402771

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