Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Antimitogenic Actions of Organic Nitrates Are Potentiated by Sildenafil and Mediated Via Activation of Protein Kinase A

Michael T. Osinski, Bernhard H. Rauch and Karsten Schrör
Molecular Pharmacology May 2001, 59 (5) 1044-1050; DOI: https://doi.org/10.1124/mol.59.5.1044
Michael T. Osinski
Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernhard H. Rauch
Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karsten Schrör
Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Migration and proliferation of vascular smooth muscle cells (SMC) in response to platelet-derived growth factor (PDGF) and other mitogens play an important role in restenosis after coronary angioplasty. Elevation of both cAMP and cGMP has been shown to inhibit SMC mitogenesis. The aim of this study was to examine the antimitogenic actions of organic nitrates and sildenafil and to clarify the role of cyclic nucleotide-dependent protein kinases (PKA, PKG) in this action. Organic nitrates [glycerol trinitrate (GTN), isosorbide 5′-mononitrate (ISMN), pentaerythrityl-tetranitrate (PETN)] and the PDE5 inhibitor sildenafil reduced PDGF-induced DNA synthesis, measured by (3H]thymidine incorporation. GTN, ISMN, and PETN acted synergistically with sildenafil (1 μM) on inhibition of PDGF-induced DNA synthesis, increase of intracellular cyclic nucleotides, and vasodilator-stimulated phosphoprotein phosphorylation. The highly selective PKA inhibitor PKI abolished these actions of sildenafil and organic nitrates, whereas the PKG inhibitors KT5823 and (Rp)-8-pCPT-cGMPS had no effect. In addition, selective activation of PKG without inhibition of PDE3 by the cGMP analog 8-pCPT-cGMP (100 μM) had no antimitogenic effect. The data suggest that 1) organic nitrates and sildenafil exert antimitogenic actions by activation of PKA via inhibition of PDE3, but not by activation of PKG and 2) that antimitogenic effects of organic nitrates are potentiated by sildenafil at therapeutic plasma levels.

Footnotes

    • Received June 1, 2000.
    • Accepted January 22, 2001.
  • Send reprint requests to: Dr. Karsten Schrör, Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität, Moorenstr. 5, 40225 Düsseldorf, Germany. E-mail: kschroer{at}uni-duesseldorf.de

  • This study was supported by the Forschungsgruppe Herz-Kreislauf e.V., Düsseldorf, Germany.

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

Log in using your username and password

Forgot your user name or password?

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

PreviousNext
Back to top

In this issue

Molecular Pharmacology: 59 (5)
Molecular Pharmacology
Vol. 59, Issue 5
1 May 2001
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Antimitogenic Actions of Organic Nitrates Are Potentiated by Sildenafil and Mediated Via Activation of Protein Kinase A
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
Citation Tools
Research ArticleArticle

Antimitogenic Actions of Organic Nitrates Are Potentiated by Sildenafil and Mediated Via Activation of Protein Kinase A

Michael T. Osinski, Bernhard H. Rauch and Karsten Schrör
Molecular Pharmacology May 1, 2001, 59 (5) 1044-1050; DOI: https://doi.org/10.1124/mol.59.5.1044

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

Antimitogenic Actions of Organic Nitrates Are Potentiated by Sildenafil and Mediated Via Activation of Protein Kinase A

Michael T. Osinski, Bernhard H. Rauch and Karsten Schrör
Molecular Pharmacology May 1, 2001, 59 (5) 1044-1050; DOI: https://doi.org/10.1124/mol.59.5.1044
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Operational Models for Receptors with Multiple Agonist Sites
  • BODIPY-cyclopamine Binding to Nluc-SMO
  • Characterization and optimization of the novel TRPM2 antagonist tatM2NX
Show more Article

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2019 by the American Society for Pharmacology and Experimental Therapeutics