Skip to main content
  • American Heart Association
  • Science Volunteer
  • Warning Signs
  • Advanced Search
  • Donate

  • Home
  • About this Journal
    • General Statistics
    • Editorial Board
    • Editors
    • Information for Advertisers
    • Author Reprints
    • Commercial Reprints
    • Customer Service and Ordering Information
  • All Issues
  • Subjects
    • All Subjects
    • Arrhythmia and Electrophysiology
    • Basic, Translational, and Clinical Research
    • Critical Care and Resuscitation
    • Epidemiology, Lifestyle, and Prevention
    • Genetics
    • Heart Failure and Cardiac Disease
    • Hypertension
    • Imaging and Diagnostic Testing
    • Intervention, Surgery, Transplantation
    • Quality and Outcomes
    • Stroke
    • Vascular Disease
  • Browse Features
    • AHA Guidelines and Statements
    • Acknowledgment of Reviewers
    • Clinical Implications
    • Clinical-Pathological Conferences
    • Controversies in Hypertension
    • Editors' Picks
    • Guidelines Debate
    • Meeting Abstracts
    • Recent Advances in Hypertension
    • SPRINT Trial: the Conversation Continues
  • Resources
    • Instructions to Reviewers
    • Instructions for Authors
    • →Article Types
    • → Submission Guidelines
      • Research Guidelines
        • Minimum Information About Microarray Data Experiments (MIAME)
      • Abstract
      • Acknowledgments
      • Clinical Implications (Only by invitation)
      • Conflict(s) of Interest/Disclosure(s) Statement
      • Figure Legends
      • Figures
      • Novelty and Significance: 1) What Is New, 2) What Is Relevant?
      • References
      • Sources of Funding
      • Tables
      • Text
      • Title Page
      • Online/Data Supplement
    • →Tips for Easier Manuscript Submission
    • → General Instructions for Revised Manuscripts
      • Change of Authorship Form
    • → Costs to Authors
    • → Open Access, Repositories, & Author Rights Q&A
    • Permissions to Reprint Figures and Tables
    • Journal Policies
    • Scientific Councils
    • AHA Journals RSS Feeds
    • International Users
    • AHA Newsroom
  • AHA Journals
    • AHA Journals Home
    • Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB)
    • Circulation
    • → Circ: Arrhythmia and Electrophysiology
    • → Circ: Genomic and Precision Medicine
    • → Circ: Cardiovascular Imaging
    • → Circ: Cardiovascular Interventions
    • → Circ: Cardiovascular Quality & Outcomes
    • → Circ: Heart Failure
    • Circulation Research
    • Hypertension
    • Stroke
    • Journal of the American Heart Association
  • Facebook
  • Twitter

  • My alerts
  • Sign In
  • Join

  • Advanced search

Header Publisher Menu

  • American Heart Association
  • Science Volunteer
  • Warning Signs
  • Advanced Search
  • Donate

Hypertension

  • My alerts
  • Sign In
  • Join

  • Facebook
  • Twitter
  • Home
  • About this Journal
    • General Statistics
    • Editorial Board
    • Editors
    • Information for Advertisers
    • Author Reprints
    • Commercial Reprints
    • Customer Service and Ordering Information
  • All Issues
  • Subjects
    • All Subjects
    • Arrhythmia and Electrophysiology
    • Basic, Translational, and Clinical Research
    • Critical Care and Resuscitation
    • Epidemiology, Lifestyle, and Prevention
    • Genetics
    • Heart Failure and Cardiac Disease
    • Hypertension
    • Imaging and Diagnostic Testing
    • Intervention, Surgery, Transplantation
    • Quality and Outcomes
    • Stroke
    • Vascular Disease
  • Browse Features
    • AHA Guidelines and Statements
    • Acknowledgment of Reviewers
    • Clinical Implications
    • Clinical-Pathological Conferences
    • Controversies in Hypertension
    • Editors' Picks
    • Guidelines Debate
    • Meeting Abstracts
    • Recent Advances in Hypertension
    • SPRINT Trial: the Conversation Continues
  • Resources
    • Instructions to Reviewers
    • Instructions for Authors
    • →Article Types
    • → Submission Guidelines
    • →Tips for Easier Manuscript Submission
    • → General Instructions for Revised Manuscripts
    • → Costs to Authors
    • → Open Access, Repositories, & Author Rights Q&A
    • Permissions to Reprint Figures and Tables
    • Journal Policies
    • Scientific Councils
    • AHA Journals RSS Feeds
    • International Users
    • AHA Newsroom
  • AHA Journals
    • AHA Journals Home
    • Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB)
    • Circulation
    • → Circ: Arrhythmia and Electrophysiology
    • → Circ: Genomic and Precision Medicine
    • → Circ: Cardiovascular Imaging
    • → Circ: Cardiovascular Interventions
    • → Circ: Cardiovascular Quality & Outcomes
    • → Circ: Heart Failure
    • Circulation Research
    • Hypertension
    • Stroke
    • Journal of the American Heart Association
Original Article

Is Flow-Mediated Dilation Nitric Oxide Mediated?

A Meta-Analysis

Daniel J. Green, Ellen A. Dawson, Hans M.M. Groenewoud, Helen Jones, Dick H.J. Thijssen
Download PDF
https://doi.org/10.1161/HYPERTENSIONAHA.113.02044
Hypertension. 2013;HYPERTENSIONAHA.113.02044
Originally published November 25, 2013
Daniel J. Green
From the Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom (D.J.G., E.A.D., H.J., D.H.J.T.); School of Sports Science, Exercise and Health, The University of Western Australia, Crawley Perth, Western Australia (D.J.G.); and Departments of Health Evidence (H.M.M.G.) and Physiology (D.H.J.T.), Radboud University Medical Center, Nijmegen, The Netherlands.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ellen A. Dawson
From the Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom (D.J.G., E.A.D., H.J., D.H.J.T.); School of Sports Science, Exercise and Health, The University of Western Australia, Crawley Perth, Western Australia (D.J.G.); and Departments of Health Evidence (H.M.M.G.) and Physiology (D.H.J.T.), Radboud University Medical Center, Nijmegen, The Netherlands.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hans M.M. Groenewoud
From the Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom (D.J.G., E.A.D., H.J., D.H.J.T.); School of Sports Science, Exercise and Health, The University of Western Australia, Crawley Perth, Western Australia (D.J.G.); and Departments of Health Evidence (H.M.M.G.) and Physiology (D.H.J.T.), Radboud University Medical Center, Nijmegen, The Netherlands.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Helen Jones
From the Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom (D.J.G., E.A.D., H.J., D.H.J.T.); School of Sports Science, Exercise and Health, The University of Western Australia, Crawley Perth, Western Australia (D.J.G.); and Departments of Health Evidence (H.M.M.G.) and Physiology (D.H.J.T.), Radboud University Medical Center, Nijmegen, The Netherlands.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dick H.J. Thijssen
From the Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom (D.J.G., E.A.D., H.J., D.H.J.T.); School of Sports Science, Exercise and Health, The University of Western Australia, Crawley Perth, Western Australia (D.J.G.); and Departments of Health Evidence (H.M.M.G.) and Physiology (D.H.J.T.), Radboud University Medical Center, Nijmegen, The Netherlands.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters

Jump to

  • Article
  • Info & Metrics
  • eLetters
Loading

Abstract

Flow-mediated dilation (FMD) is a noninvasive index of endothelial function and vascular health in humans. Studies examining the role of nitric oxide (NO) are not conclusive. In this article, we quantified the contribution of NO in FMD of conduit arteries and explored the effect of the protocol (ie, distal cuff, ≈5-minute ischemia) and method of analysis (ie, automated and continuous edge detection) on the NO dependency of this test. A systematic review and 3-stage meta-analysis of published crossover studies that measured FMD under local infusion of saline or the NO synthase blocker NGmonomethyl-L-arginine (L-NMMA) was undertaken. Twenty studies met the inclusion criteria for stage 1 (374 individual comparisons). The meta-analyzed outcome was the difference in FMD between infusion of saline (ie, FMDsaline) and NO synthase blocker (ie, FMDL-NMMA). Overall, FMDsaline was 8.2% (95% confidence interval [CI], 6.8%–9.6%) compared with FMDL-NMMA of 3.7% (95% CI, 3.1%–4.3%; P<0.001). Stage 2 analysis focused on studies that used the most commonly adopted approach in healthy volunteers (ie, distal cuff placement, ≈5-minute occlusion), which similarly revealed a significant NO contribution to FMD (FMDsaline, 6.5% [95% CI, 5.7%–7.3%]; FMDL-NMMA, 0.9% [95% CI, 0.5%–1.3%]; P<0.001). Stage 3 meta-analyzed the studies that adopted the commonly adopted approach and automated, continuous method of analysis, which also revealed a significant contribution of NO to the FMD (FMDsaline, 6.9% [95% CI, 6.0%–7.8%]; FMDL-NMMA, 2.4% [95% CI, 1.1%–3.7%]; P<0.001). This comprehensive analysis demonstrates that FMD of conduit arteries in humans is, at least in part, mediated by NO.

  • conduit artery
  • FMD protocol
  • NGmonomethy-L-arginine
  • nitric oxide
  • shear stress
  • vascular
  • Received July 13, 2013.
  • Revision received August 2, 2013.
  • Accepted October 27, 2013.
  • © 2013 American Heart Association, Inc.
Back to top
Next Article

Current Issue

Hypertension
May 2018, Volume 71, Issue 5
  • Table of Contents
Next Article

Jump to

  • Article
  • Info & Metrics
  • eLetters

Article Tools

  • Print
  • Citation Tools
    Is Flow-Mediated Dilation Nitric Oxide Mediated?
    Daniel J. Green, Ellen A. Dawson, Hans M.M. Groenewoud, Helen Jones and Dick H.J. Thijssen
    Hypertension. 2013;HYPERTENSIONAHA.113.02044, originally published November 25, 2013
    https://doi.org/10.1161/HYPERTENSIONAHA.113.02044

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
  • Article Alerts
    Log in to Email Alerts with your email address.
  • Save to my folders

Share this Article

  • Email

    Thank you for your interest in spreading the word on Hypertension.

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    Is Flow-Mediated Dilation Nitric Oxide Mediated?
    (Your Name) has sent you a message from Hypertension
    (Your Name) thought you would like to see the Hypertension web site.
  • Share on Social Media
    Is Flow-Mediated Dilation Nitric Oxide Mediated?
    Daniel J. Green, Ellen A. Dawson, Hans M.M. Groenewoud, Helen Jones and Dick H.J. Thijssen
    Hypertension. 2013;HYPERTENSIONAHA.113.02044, originally published November 25, 2013
    https://doi.org/10.1161/HYPERTENSIONAHA.113.02044
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Related Articles

Cited By...

Subjects

  • Imaging and Diagnostic Testing
    • Imaging
  • Basic, Translational, and Clinical Research
    • Endothelium/Vascular Type/Nitric Oxide

Hypertension

  • About Hypertension
  • Instructions for Authors
  • AHA CME
  • Guidelines and Statements
  • Permissions
  • Journal Policies
  • Email Alerts
  • Open Access Information
  • AHA Journals RSS
  • AHA Newsroom

Editorial Office Address:
7272 Greenville Ave.
Dallas, TX 75231
email: hypertension@heart.org

Information for:
  • Advertisers
  • Subscribers
  • Subscriber Help
  • Institutions / Librarians
  • Institutional Subscriptions FAQ
  • International Users
American Heart Association Learn and Live
National Center
7272 Greenville Ave.
Dallas, TX 75231

Customer Service

  • 1-800-AHA-USA-1
  • 1-800-242-8721
  • Local Info
  • Contact Us

About Us

Our mission is to build healthier lives, free of cardiovascular diseases and stroke. That single purpose drives all we do. The need for our work is beyond question. Find Out More about the American Heart Association

  • Careers
  • SHOP
  • Latest Heart and Stroke News
  • AHA/ASA Media Newsroom

Our Sites

  • American Heart Association
  • American Stroke Association
  • For Professionals
  • More Sites

Take Action

  • Advocate
  • Donate
  • Planned Giving
  • Volunteer

Online Communities

  • AFib Support
  • Garden Community
  • Patient Support Network
  • Professional Online Network

Follow Us:

  • Follow Circulation on Twitter
  • Visit Circulation on Facebook
  • Follow Circulation on Google Plus
  • Follow Circulation on Instagram
  • Follow Circulation on Pinterest
  • Follow Circulation on YouTube
  • Rss Feeds
  • Privacy Policy
  • Copyright
  • Ethics Policy
  • Conflict of Interest Policy
  • Linking Policy
  • Diversity
  • Careers

©2018 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. The American Heart Association is a qualified 501(c)(3) tax-exempt organization.
*Red Dress™ DHHS, Go Red™ AHA; National Wear Red Day ® is a registered trademark.

  • PUTTING PATIENTS FIRST National Health Council Standards of Excellence Certification Program
  • BBB Accredited Charity
  • Comodo Secured