Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
March-2015 Volume 11 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2015 Volume 11 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist

  • Authors:
    • Ji‑Min Sun
    • Chun‑Miao Wang
    • Zeng Guo
    • Yu‑Yu Hao
    • Yang‑Jing Xie
    • Jian Gu
    • Ai‑Ling Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Emergency, The First People's Hospital of Hefei, Hefei, Anhui 230051, P.R. China, Department of Cardiology, The First People's Hospital of Hefei, Hefei, Anhui 230051, P.R. China
  • Pages: 1845-1850
    |
    Published online on: November 20, 2014
       https://doi.org/10.3892/mmr.2014.2988
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Cardiac hypertrophy is a compensatory mechanism that occurs in conjunction with cardiovascular diseases. Although hypertrophy of the myocardium provides certain benefits during the early stages of cardiovascular disease, prolonged hypertrophy is potentially harmful to the heart and can result in arrhythmia and heart failure. The aim of this study was to investigate whether an ATP‑sensitive K+ (KATP) channel agonist was capable of reducing isoproterenol (Iso)‑induced cardiac hypertrophy and modulating myocardial connexin43 (Cx43) expression. Fifty male Sprague Dawley rats were randomly assigned to five groups: Normal, vehicle, nicorandil, glibenclamide and nicorandil plus glibenclamide. Rats in the four treatment groups received Iso injection for seven days, followed by administration with saline, nicorandil, glibenclamide or a combination of nicorandil and glibenclamide, respectively, for four weeks. Cardiac hypertrophy was then evaluated by measuring body weight, heart weight and left‑ventricular weight, and plasma B‑type natriuretic peptide levels were evaluated by ELISA. Immunocytochemistry and a reverse transcription‑polymerase chain reaction were performed to detect the spatial distribution and gene expression of myocardial Cx43, respectively. The KATP channel agonist nicorandil markedly attenuated the degree of myocardial hypertrophy induced by Iso as compared with the vehicle group. Myocardial Cx43 expression was significantly decreased and redistributed following cardiac hypertrophy. The decrease and redistribution of Cx43 was reduced following treatment with the KATP channel agonist nicorandil. Addition of the KATP channel blocker glibenclamide eliminated the beneficial effects of nicorandil against hypertrophy and on connexin43. In conclusion, the present study indicated that chronic use of KATP channel agonists following cardiac hypertrophy can attenuate ventricular remodeling and upregulate the expression level and spatial distribution of Cx43.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Weber KT, Anversa P, Armstrong PW, et al: Remodeling and reparation of the cardiovascular system. J Am Coll Cardiol. 20:3–16. 1992. View Article : Google Scholar : PubMed/NCBI

2 

Verdecchia P, Carini G and Circo A; MAVI (MAssa Ventricolare sinistra nell'Ipertensione) Study Group. Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study. J Am Coll Cardiol. 38:1829–1835. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Choudhary R, Mishra KP and Subramanyam C: Prevention of isoproterenol-induced cardiac hypertrophy by eugenol, an antioxidant. Indian J Clin Biochem. 21:107–113. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Rajesh KG, Sasaguri S, Suzuki R, Xing Y and Maeda H: Ischemic preconditioning prevents reperfusion heart injury in cardiac hypertrophy by activation of mitochondrial KATP channels. Int J Cardiol. 96:41–49. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Lee TM, Lin MS and Chang NC: Effect of ATP-sensitive potassium channel agonists on ventricular remodeling in healed rat infarcts. J Am Coll Cardio. 51:1309–1318. 2008. View Article : Google Scholar

6 

Ennis IL, Escudero EM, Console GM, et al: Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition. Hypertension. 41:1324–1329. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Frohlich ED: State of the Art lecture. Risk mechanisms in hypertensive heart disease. Hypertension. 34:782–789. 1999. View Article : Google Scholar : PubMed/NCBI

8 

Joyner RW: Effects of the discrete pattern of electrical coupling on propagation through an electrical syncytium. Circ Res. 50:192–200. 1982. View Article : Google Scholar : PubMed/NCBI

9 

Danik SB, Liu F, Zhang J, Suk HJ, Morley GE, Fishman GI and Gutstein DE: Modulation of cardiac gap junction expression and arrhythmic susceptibility. Circ Res. 95:1035–1041. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Boengler K, Dodoni G, Rodriguez-Sinovas A, et al: Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning. Cardiovasc Res. 67:234–244. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Roell W, Lewalter T, Sasse P, et al: Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature. 450:819–824. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Rottlaender D, Boengler K, Wolny M, et al: Connexin 43 acts as a cytoprotective mediator of signal transduction by stimulating mitochondrial KATP channels in mouse cardiomyocytes. J Clin Invest. 120:1441–1453. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Wang A, Chen F, Xie Y, Guo Z and Yu Y: Protective mechanism of nicorandil on rat myocardial ischemia-reperfusion. J Cardiovasc Med (Hagerstown). 13:511–515. 2012. View Article : Google Scholar

14 

de Lemos JA, McGuire DK and Drazner MH: B-type natriuretic peptide in cardiovascular disease. Lancet. 362:316–322. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Tang Y, Wang M, Le X, et al: Antioxidant and cardioprotective effects of Danshensu (3-(3,4-dihydroxyphenyl)-2-hydroxy-propanoic acid from Salvia miltiorrhiza) on isoproterenol-induced myocardial hypertrophy in rats. Phytomedicine. 18:1024–1030. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Pfeffer MA and Braunwald E: Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation. 81:1161–1172. 1990. View Article : Google Scholar : PubMed/NCBI

17 

Sakai K: Nicorandil: animal pharmacology. Am J Cardiol. 63:2J–10J. 1989. View Article : Google Scholar : PubMed/NCBI

18 

Lee TM, Lin CC, Lien HY and Chen CC: K ATP channel agonists preserve connexin43 protein in infarcted rats by a protein kinase C-dependent pathway. J Cell Mol Med. 16:776–788. 2012. View Article : Google Scholar

19 

Guéant Rodriguez RM, Spada R, Pooya S, et al: Homocysteine predicts increased NT-pro-BNP through impaired fatty acid oxidation. Int J Cardiol. 167:768–775. 2013. View Article : Google Scholar

20 

Swedberg K, Cleland J, Dargie H, et al: Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology: Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J. 26:1115–1140. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Kimura T, Kitamura H, Inoue K, et al: Effects of nicorandil on the reduction of BNP levels in patients with chronic kidney disease. Clin Exp Nephrol. 15:854–860. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Kanno S and Saffitz JE: The role of myocardial gap junctions in electrical conduction and arrhythmogenesis. Cardiovasc Pathol. 10:169–177. 2001. View Article : Google Scholar : PubMed/NCBI

23 

Egashira K, Nishii K, Nakamura K, Kumai M, Morimoto S and Shibata Y: Conduction abnormality in gap junction protein connexin45-deficient embryonic stem cell-derived cardiac myocytes. Anat Rec A Discov Mol Cell Evol Biol. 280:973–979. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Wang Y and Hill JA: Electrophysiological remodeling in heart failure. J Mol Cell Cardiol. 48:619–632. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Ohara T, Ohara K, Cao JM, et al: Increased wave break during ventricular fibrillation in the epicardial border zone of hearts with healed myocardial infarction. Circulation. 103:1465–1472. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Naitoh K, Ichikawa Y, Miura T, et al: MitoKATP channel activation suppresses gap junction permeability in the ischemic myocardium by an ERK-dependent mechanism. Cardiovasc Res. 70:374–383. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Amino M, Yoshioka K, Tanabe T, et al: Heavy ion radiation up-regulates Cx43 and ameliorates arrhythmogenic substrates in hearts after myocardial infarction. Cardiovasc Res. 72:412–421. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Döring G: Antianginal and anti-ischemic efficacy of nicorandil in comparison with isosorbide-5-mononitrate and isosorbide dinitrate: results from two multicenter, double-blind, randomized studies with stable coronary heart disease patients. J Cardiovasc Pharmacol. 20(Suppl 3): S74–S81. 1992. View Article : Google Scholar : PubMed/NCBI

29 

The SWAN Study Group. Comparison of the antiischaemic and antianginal effects of nicorandil and amlodipine in patients with symptomatic stable angina pectoris: the SWAN study. J Clin Basic Cardiol. 2:213–217. 1999.

30 

Di Somma S, Liguori V, Petitto M, Carotenuto A, Bokor D, de Divitiis O and de Divitiis M: A double-blind comparison of nicorandil and metoprolol in stable effort angina pectoris. Cardiovasc Drugs Ther. 7:119–123. 1993. View Article : Google Scholar : PubMed/NCBI

31 

Zhu WL, Shan YD, Guo JX, et al: Double-blind, multicenter, active-controlled, randomized clinical trial to assess the safety and efficacy of orally administered nicorandil in patients with stable angina pectoris in China. Circ J. 71:826–833. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Baines CP, Liu GS, Birincioglu M, Critz SD, Cohen MV and Downey JM: Ischemic preconditioning depends on interaction between mitochondrial KATP channels and actin cytoskeleton. Am J Physiol. 276:H1361–H1368. 1999.PubMed/NCBI

33 

Sugimoto K, Ito H, Iwakura K, et al: Intravenous nicorandil in conjunction with coronary reperfusion therapy is associated with better clinical and functional outcomes in patients with acute myocardial infarction. Circ J. 67:295–300. 2003. View Article : Google Scholar : PubMed/NCBI

34 

Garlid KD, Paucek P, Yarov-Yarovoy V, et al: Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive K+ channels. Possible mechanism of cardioprotection. Circ Res. 81:1072–1082. 1997. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Sun JM, Wang CM, Guo Z, Hao YY, Xie YJ, Gu J and Wang AL: Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist. Mol Med Rep 11: 1845-1850, 2015.
APA
Sun, J., Wang, C., Guo, Z., Hao, Y., Xie, Y., Gu, J., & Wang, A. (2015). Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist. Molecular Medicine Reports, 11, 1845-1850. https://doi.org/10.3892/mmr.2014.2988
MLA
Sun, J., Wang, C., Guo, Z., Hao, Y., Xie, Y., Gu, J., Wang, A."Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist". Molecular Medicine Reports 11.3 (2015): 1845-1850.
Chicago
Sun, J., Wang, C., Guo, Z., Hao, Y., Xie, Y., Gu, J., Wang, A."Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist". Molecular Medicine Reports 11, no. 3 (2015): 1845-1850. https://doi.org/10.3892/mmr.2014.2988
Copy and paste a formatted citation
x
Spandidos Publications style
Sun JM, Wang CM, Guo Z, Hao YY, Xie YJ, Gu J and Wang AL: Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist. Mol Med Rep 11: 1845-1850, 2015.
APA
Sun, J., Wang, C., Guo, Z., Hao, Y., Xie, Y., Gu, J., & Wang, A. (2015). Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist. Molecular Medicine Reports, 11, 1845-1850. https://doi.org/10.3892/mmr.2014.2988
MLA
Sun, J., Wang, C., Guo, Z., Hao, Y., Xie, Y., Gu, J., Wang, A."Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist". Molecular Medicine Reports 11.3 (2015): 1845-1850.
Chicago
Sun, J., Wang, C., Guo, Z., Hao, Y., Xie, Y., Gu, J., Wang, A."Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist". Molecular Medicine Reports 11, no. 3 (2015): 1845-1850. https://doi.org/10.3892/mmr.2014.2988
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team