Is flow-mediated dilation nitric oxide mediated?: A meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of human crossover experimental studies
PubMed 24277765 · doi:10.1161/HYPERTENSIONAHA.113.02044
What was done
A systematic review and three-stage meta-analysis of published crossover trials was performed to assess the nitric oxide (NO) dependency of human conduit artery flow-mediated dilation (FMD). Studies compared FMD under local intra-arterial infusion of saline control versus the NO synthase blocker L-NMMA. Sub-analyses examined the impact of standard protocol features (distal cuff placement, ~5-minute ischemia) and analysis techniques (automated continuous edge detection).
What was found
Across 20 studies (374 comparisons in Stage 1), FMD with saline was 8.2% (95% CI, 6.8% to 9.6%) compared with 3.7% (95% CI, 3.1% to 4.3%; P < 0.001) under L-NMMA infusion. In Stage 2 (standard distal cuff and ~5-minute occlusion in healthy volunteers), saline FMD was 6.5% (95% CI, 5.7% to 7.3%) versus 0.9% (95% CI, 0.5% to 1.3%; P < 0.001) with L-NMMA. In Stage 3 (standard protocol plus automated edge detection), saline FMD was 6.9% (95% CI, 6.0% to 7.8%) versus 2.4% (95% CI, 1.1% to 3.7%; P < 0.001) with L-NMMA.
Why it matters
This review validates flow-mediated dilation as a physiological bioassay largely dependent on endothelial nitric oxide release, reinforcing its clinical and research utility for assessing endothelial health in humans.
Limits
The abstract does not state the total count of unique human participants, only the number of studies and comparisons. Residual dilation remained despite L-NMMA blockade (ranging from 0.9% to 3.7%), indicating that non-NO vasodilatory pathways contribute to the response or that pharmacological blockade was incomplete. Specific clinical sub-populations (such as patients with cardiovascular disease) were not broken out in the abstract results.
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