Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • 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
  • Log out
  • My Cart

Search

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

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
OtherCARDIOVASCULAR PHARMACOLOGY

Acute Effects of Nitric Oxide and Cyclic GMP on Human Myocardial Contractility

Markus Flesch, Heiko Kilter, Bodo Cremers, Olaf Lenz, Michael Südkamp, Ferdinand Kuhn-Regnier and Michael Böhm
Journal of Pharmacology and Experimental Therapeutics June 1997, 281 (3) 1340-1349;
Markus Flesch
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heiko Kilter
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bodo Cremers
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olaf Lenz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Südkamp
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ferdinand Kuhn-Regnier
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Böhm
  • 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

Evidence that the activity of nitric oxide synthase and the generation of nitric oxide (NO) within the myocardium are enhanced in several cardiovascular disorders is increasing. Findings whether NO exerts a direct effect on cardiac contractility are contradictory. Therefore, the direct effect of the NO donor sodium nitroprusside (SNP) on isometric force of contraction of human atrial and ventricular myocardium was investigated, and the question was addressed whether the effects of NO on cardiac contractility are mediated viacGMP. Experiments were performed on isolated electrically driven (1Hz, 37°C) human right atrial trabecula and left ventricular papillary muscle preparations from nonfailing and terminally failing hearts. SNP led to a concentration-dependent decrease of force of contraction (FOC) with a maximum effect at 100 μmol/l. In atrial trabecula, SNP (100 μmol/l) caused an acute decrease in basal FOC as well as in FOC after application of isoprenaline or IBMX by 12.5 ± 5% (P < .05), 16.6 ± 3.7% (P < .05) and 18.3 ± 4.2% (P < .05), respectively. The negative inotropic effects could be attenuated by the guanylyl cyclase inhibitor methylene blue. In papillary muscle preparations, NO release caused a maximum decrease in basal and in isoprenaline-enhanced FOC of 11.0 ± 1.9% (P < .05) and 23.6 ± 1.5% (P < .05), respectively. In the presence of isoprenaline, the reduction of FOC was less pronounced in failing than in nonfailing papillary muscles. 8-bromo-cGMP caused a 38.2 ± 5.2% decrease in atrial trabecula contractility. Both SNP and 8-bromo-cGMP caused a shortening of the contractile twitch with a premature onset of relaxation. As determined by radioimmunoassay, exposure of atrial trabecula to SNP (100 μmol) led to a 6-fold increase in myocardial cGMP concentrations, which could be attenuated by methylene blue. In conclusion, NO exerts a negative inotropic effect on human atrial and ventricular myocardium which seems to be mediatedvia generation of cGMP. The release of NO within the myocardium in a variety of cardiovascular disorders might explain decreases in cardiac contractility. The control of NO release could be an important target for future therapeutical interventions in these pathological conditions.

Footnotes

  • Send reprint requests to: M.Flesch, M.D., Klinik III für Innere Medizin der Universität zu Köln, Joseph-Stelzmann-Str. 9, 50924 Köln, Germany.

  • ↵1 Experimental work was supported by the Deutsche Forschungsgemeinschaft (to M.B.). This work contains data of the Doctoral Thesis of H.K. (University of Cologne, in preparation).

  • ↵2 Recipient of the Gerhard Hess Program of the Deutsche Forschungsgemeinschaft.

  • Abbreviations:
    FOC
    force of contraction
    NO
    nitric oxide
    NOS
    nitric oxide synthase
    cNOS
    constitutive nitric oxide synthase
    iNOS
    inducible nitric oxide synthase
    MB
    methylene blue
    cGMP
    cyclic 3′-5′-guanosine monophosphate
    SNP
    sodium nitroprusside
    IBMX
    isobutylmethylxanthine
    R-PIA
    R-N6-phenylisopropyladenosine
    KCN
    potassium cyanide
    l-NMMA
    NG-monomethyl-l-arginine
    • Received July 24, 1996.
    • Accepted February 14, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics
Vol. 281, Issue 3
1 Jun 1997
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics 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.
Acute Effects of Nitric Oxide and Cyclic GMP on Human Myocardial Contractility
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OtherCARDIOVASCULAR PHARMACOLOGY

Acute Effects of Nitric Oxide and Cyclic GMP on Human Myocardial Contractility

Markus Flesch, Heiko Kilter, Bodo Cremers, Olaf Lenz, Michael Südkamp, Ferdinand Kuhn-Regnier and Michael Böhm
Journal of Pharmacology and Experimental Therapeutics June 1, 1997, 281 (3) 1340-1349;

Citation Manager Formats

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

Share
OtherCARDIOVASCULAR PHARMACOLOGY

Acute Effects of Nitric Oxide and Cyclic GMP on Human Myocardial Contractility

Markus Flesch, Heiko Kilter, Bodo Cremers, Olaf Lenz, Michael Südkamp, Ferdinand Kuhn-Regnier and Michael Böhm
Journal of Pharmacology and Experimental Therapeutics June 1, 1997, 281 (3) 1340-1349;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Preconditioning of Rat Heart with Monophosphoryl Lipid A: A Role for Nitric Oxide
  • TAS-301, an Inhibitor of Smooth Muscle Cell Migration and Proliferation, Inhibits Intimal Thickening after Balloon Injury to Rat Carotid Arteries
  • Identification of Low Molecular Weight GP IIb/IIIa Antagonists That Bind Preferentially to Activated Platelets
Show more CARDIOVASCULAR PHARMACOLOGY

Similar Articles

Advertisement
  • 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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics