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Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
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Related Experiment Video

Updated: May 5, 2026

Ultrasound Assessment of Flow-Mediated Dilation of the Brachial and Superficial Femoral Arteries in Rats
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Is flow-mediated dilation nitric oxide mediated?: A meta-analysis.

Daniel J Green1, Ellen A Dawson, Hans M M Groenewoud

  • 1Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Tom Reilly Bldg, Byrom St, L3 3AF Liverpool, United Kingdom. d.j.green@ljmu.ac.uk.

Hypertension (Dallas, Tex. : 1979)
|November 27, 2013
PubMed
Summary

Flow-mediated dilation (FMD) assesses vascular health. This study confirms nitric oxide (NO) significantly contributes to FMD in human arteries, clarifying its role in endothelial function.

Keywords:
FMD protocolNGmonomethy-L-arginineconduit arterynitric oxideshear stressvascular

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Area of Science:

  • Cardiovascular Physiology
  • Endothelial Function Research
  • Vascular Health Assessment

Background:

  • Flow-mediated dilation (FMD) is a key noninvasive indicator of endothelial function and vascular health in humans.
  • Previous studies on the role of nitric oxide (NO) in FMD have yielded inconclusive results.
  • Understanding the precise contribution of NO to FMD is crucial for accurate vascular health assessment.

Purpose of the Study:

  • To quantify the contribution of nitric oxide (NO) to flow-mediated dilation (FMD) in conduit arteries.
  • To investigate the influence of common FMD protocols (distal cuff, ~5-minute ischemia) and analysis methods (automated edge detection) on NO dependency.
  • To provide a comprehensive analysis of NO's role in FMD through a systematic review and meta-analysis.

Main Methods:

  • A systematic review and three-stage meta-analysis of published crossover studies were conducted.
  • Studies involving local infusion of saline or the NO synthase blocker N(G)monomethyl-L-arginine (L-NMMA) were included.
  • Meta-analysis compared FMD measurements under saline (FMD(saline)) versus L-NMMA (FMD(L-NMMA)) conditions.

Main Results:

  • Across all included studies, FMD(saline) was 8.2% compared to FMD(L-NMMA) of 3.7% (P<0.001), indicating a significant NO contribution.
  • Analysis of studies using standard protocols (distal cuff, ~5-minute occlusion) showed FMD(saline) of 6.5% versus FMD(L-NMMA) of 0.9% (P<0.001).
  • Studies employing standard protocols and automated analysis also demonstrated a significant NO contribution (FMD(saline), 6.9%; FMD(L-NMMA), 2.4%; P<0.001).

Conclusions:

  • This meta-analysis confirms that nitric oxide (NO) plays a significant, albeit partial, role in mediating flow-mediated dilation (FMD) in human conduit arteries.
  • The findings support the validity of FMD as an index of endothelial function, with a quantifiable NO-dependent component.
  • Standardized protocols and analysis methods consistently highlight the importance of NO in FMD measurements.