Endothelial dysfunction

Endothelial dysfunction is when the thin inner lining of your blood vessels (the endothelium) stops keeping them healthy. The classic problem: it makes too little usable nitric oxide (NO), the main signal that relaxes vessels and tamps down inflammation, produced by an enzyme called eNOS. Normally, the push of blood flow (shear stress) switches on eNOS, which releases NO that tells the vessel's muscle to relax. In a dysfunctional vessel, that response is blunted. Reactive oxygen species, especially superoxide, mop up the NO before it can work, and eNOS itself 'uncouples', making oxidants instead of NO. Doctors measure this with flow-mediated dilation (FMD) of the arm's brachial artery, a non-invasive ultrasound test first validated by Celermajer et al. (1992): a cuff is inflated to create shear stress, and the percent widening of the artery shows NO-driven dilation. Beyond poor dilation, a sick endothelium gets sticky, recruiting white cells and platelets and turning clot-prone, which is one of the earliest steps in plaque buildup, years or decades before an artery visibly narrows (Bonetti et al., 2003). FMD drops with age even in healthy people, and lower FMD independently predicts heart attacks and strokes. Whether boosting FMD with treatment actually cuts those events is still being studied.

Last reviewed: June 22, 2026

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