Document Detail


Spironolactone diminishes spontaneous ventricular premature beats by reducing HCN4 protein expression in rats with myocardial infarction.
MedLine Citation:
PMID:  21468609     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hyperpolarization-activated current (If) is the major ionic current contributing to the spontaneous diastolic depolarization of cardiac sinus node pacemaker cells. It is mediated by hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. However, several observations support a potential role of HCN channels in the arrhythmogenesis of working myocardium under pathological conditions. Spironolactone, a classic aldosterone blocker, has been proved to prevent spontaneous ventricular arrhythmias after myocardial infarction (MI). Here, we examined the effect of spironolactone on the expression of HCN channels and ventricular premature beats (VPBs) using a rat MI model. Sprague-Dawley rats were divided into a sham-operated group and MI groups treated with intragastric administration of saline or spironolactone (80 µg/kg/day) for 7 days immediately after ligation of the left coronary artery. Compared to the sham group, HCN2 and HCN4 protein levels were increased in MI rats. Treatment with spironolactone prevented the MI-induced increase of HCN4 protein levels (1.47 ± 0.16 vs. 1.81 ± 0.21, P<0.05). MI rats exhibited a marked increase of VPBs compared to the sham group (104 ± 17 vs. 3 ± 1 VPBs/h, P < 0.05). This the increase was reduced by spironolactone (55 ± 14 vs. 104 ± 17 VPBs/h, P < 0.05). Moreover, If current inhibitor (ivabradine, 0.5 mg/kg) further decreased the occurrence of VPBs in the control and spironolactone groups to the same level (54 ± 13 vs. 49 ± 8 VPBs/h, P > 0.05). In conclusion, spironolactone may prevent ischemia-induced VPBs by reducing HCN4 protein expression to basal levels.
Authors:
Tao Song; Jing Yang; Yuan Yao; Haitao Li; Yongjun Chen; Jun Zhang; Congxin Huang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-14
Journal Detail:
Title:  Molecular medicine reports     Volume:  4     ISSN:  1791-3004     ISO Abbreviation:  Mol Med Rep     Publication Date:    2011 May-Jun
Date Detail:
Created Date:  2011-04-06     Completed Date:  2011-07-13     Revised Date:  2013-02-22    
Medline Journal Info:
Nlm Unique ID:  101475259     Medline TA:  Mol Med Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  569-73     Citation Subset:  IM    
Affiliation:
Department of Cardiology, Renmin Hospital of Wuhan University, and Cardiovascular Research Institute,Wuhan University, Wuhan 430060, PR China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzazepines / pharmacology
Blotting, Western
Heart Rate / drug effects
Ion Channels / metabolism
Male
Myocardial Infarction / complications*,  drug therapy*,  physiopathology,  ultrasonography
Potassium Channels / metabolism*
Rats
Rats, Sprague-Dawley
Spironolactone / pharmacology,  therapeutic use*
Survival Analysis
Ventricular Premature Complexes / complications*,  drug therapy*,  physiopathology,  ultrasonography
Chemical
Reg. No./Substance:
0/Benzazepines; 0/HCN2 potassium channel; 0/HCN4 protein, rat; 0/Ion Channels; 0/Potassium Channels; 155974-00-8/ivabradine; 52-01-7/Spironolactone

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