The endothelium, the single layer of cells lining every artery, vein and capillary you have, makes nitric oxide, a gas that signals the muscle in the vessel wall to relax so the vessel widens. It sets blood pressure and flow, and how much you make is among the first things to decline before stiff arteries and atherosclerosis. You raise it two ways: exercise, where faster blood dragging over the lining is the signal, and nitrate-rich vegetables like beetroot and leafy greens.
You lose it with age and with hours of unbroken sitting. A poor flow-mediated-dilation reading, the standard way to measure it, predicts later heart trouble. And the popular L-arginine NO-booster supplements, which supply the raw material, mostly do not deliver.
Findings & Outcomes
What It Is
The endothelium is the single layer of cells lining the inside of every artery, vein and capillary you have. For most of medicine's history it was treated as inert, a passive surface for blood to slide over. It is an active organ that responds to the blood moving across it and controls the vessel underneath.
Its central output is a gas. When the lining is working it makes small amounts of nitric oxide and releases it into the muscular wall of the vessel, where it signals that muscle to relax. A relaxed wall is a wider vessel, more flow, and lower pressure. A lining that has stopped making enough nitric oxide is the first step, before any blockage a scan could show, toward stiff arteries, high blood pressure and atherosclerosis.
The gas lasts only seconds, so you cannot store it or dose it directly in any useful way. What matters is how much your lining is making, moment to moment, where it is needed. The standard way to read that in a living person is flow-mediated dilation: a cuff blocks blood flow in the arm for a few minutes, and when it releases, the surge of returning blood widens the artery. How much it widens measures how much nitric oxide the lining can produce on demand, and it is the number nearly every study on this page uses.
How It Works
How the Vessel Lining Works
1The lining releases nitric oxide, and the vessel relaxes
The endothelium continuously makes small amounts of nitric oxide using an enzyme called eNOS, which builds the gas from the amino acid L-arginine. The gas diffuses the short distance into the muscle of the vessel wall and signals it to relax, so the vessel widens. This was shown directly in 1980: a ring of artery relaxes to its trigger only while the inner lining is intact, and rub the lining off and the same trigger does nothing.
2Faster blood switches the enzyme on, through shear stress
The signal that raises eNOS activity is physical. As blood moves faster over the lining it drags along the wall, a force called shear stress, and shear stress is the main trigger for making nitric oxide. Anything that moves more blood, faster, over the lining raises it, which is why exercise and heat improve how vessels widen and why sitting still lowers it.
3Food nitrate feeds a second supply route
A second route makes nitric oxide without eNOS. Nitrate from vegetables is concentrated in saliva, and bacteria on the tongue turn it into nitrite. The body then converts nitrite into nitric oxide, and it does so best where oxygen is low, which is where a vessel is most starved of it.
Two of these routes are worth following out to the pages that act on them. The shear-stress route is why movement matters: faster blood means more drag on the lining means more nitric oxide, the machinery under cardiovascular training, walking and heat. The food-nitrate route runs through the mouth, and the tongue-bacteria step is covered on the oral microbiome page, while the food dose that works, and who gains most from it, is on the dietary nitrate and beetroot page. Antibacterial mouthwash blunts this second route by killing the tongue bacteria the pathway depends on.
What Raises and Lowers It
The levers that move nitric oxide are ordinary.
The Research & Studies
Everything here is based on the research we have collected and checked, sorted into groups and ordered with the strongest evidence first. Click any claim to open the studies behind it.
How it works
The lining releases nitric oxide to widen the vessel
Blood vessels widen because their inner lining releases a gas, nitric oxide, that tells the muscle in the vessel wall to relax. Strip that lining away and the same trigger does nothing.
In 1980 Furchgott and Zawadzki showed that a ring of rabbit artery relaxes to acetylcholine only when its inner endothelial layer is intact; rub the lining off and the response disappears. The lining was releasing a short-lived signal they called endothelium-derived relaxing factor, later identified as nitric oxide, made by the enzyme eNOS and diffusing to the smooth muscle to widen the vessel. The demonstration was in isolated animal tissue and the identity of the factor came from later work, but it is the foundation of everything on this page: the vessel wall is an active organ that controls its own diameter.
The study · 1
Furchgott & Zawadzki, the obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine · Nature 1980;288(5789):373-376
Mouth bacteria turn food nitrate into nitric oxide
There is a second way to make nitric oxide besides the enzyme in your vessels: eat nitrate-rich vegetables. Mouth bacteria turn the nitrate into nitrite, and the body turns that into nitric oxide.
Alongside the eNOS enzyme, the body runs a diet-based route. Nitrate from leafy greens and beetroot is absorbed, concentrated in the salivary glands, and reduced to nitrite by bacteria on the tongue; nitrite is then converted to nitric oxide in the blood and tissues, a conversion that works best where oxygen is low, which is exactly where a vessel most needs to widen. Antiseptic mouthwash, by killing those bacteria, blunts this route. Lundberg and colleagues describe the pathway in a 2008 review; it is the mechanism behind the beetroot blood-pressure findings rather than a clinical result itself.
The study · 1
Lundberg et al., the nitrate-nitrite-nitric oxide pathway in physiology and therapeutics · Nat Rev Drug Discov 2008;7(2):156-167
Blocking blood-flow shear stopped exercise from improving dilation
Regular exercise improved how well arteries widen, and the trigger was the friction of faster blood flowing over the vessel lining during exercise. When that friction was blocked in one arm, the improvement did not happen there.
Tinken and colleagues trained healthy young men and measured flow-mediated dilation at weeks two, four and six, where it rose progressively (P<0.001). To test the mechanism they attenuated the exercise-induced rise in blood flow, and therefore in wall shear stress, in one limb using a cuff; the cuffed limb did not show the improvement the free limb did. This is the demonstration that shear stress, the drag of blood moving over the endothelium, is the signal that upregulates eNOS and improves function with training. The sample was small and male, so it is a mechanism study rather than an outcome one.
Who this may not transfer to:Measured in young healthy men only. Endothelial responses to training, and the age at which function declines, differ by sex, so the size of the same adaptation in women is not established by this study.
The study · 1
Tinken et al., shear stress mediates endothelial adaptations to exercise training in humans · Hypertension 2010;55(2):312-318
Dilation declines with age, from about 40 in men
The ability of arteries to widen declines with age. In men it starts falling around 40; in women it holds up until the early 50s, around menopause, and then drops faster.
Celermajer and colleagues measured flow-mediated dilation in 238 healthy people, 103 men and 135 women aged 15 to 72. Function declined with age overall (r = -0.34, P<0.0001). The decline began around age 40 in men, at about 0.21% per year, and later in women, from the early 50s but then steeper, at about 0.49% per year, a pattern consistent with estrogen supporting endothelial nitric oxide until menopause. Being cross-sectional, it compares different people of different ages rather than following individuals, so generational differences and the risk factors that accumulate with age are mixed into the ageing signal.
The study · 1
Celermajer et al., aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women · J Am Coll Cardiol 1994;24(2):471-476
Heart And Vascular
Dietary nitrate lowered top blood pressure about 4 mmHg
Beetroot juice and other nitrate-rich foods lowered the top blood-pressure number by about 4 to 5 mmHg across 16 trials, a change on the order of a single blood-pressure tablet. The bottom number moved less and not reliably.
Siervo and colleagues pooled 16 randomized controlled trials, 254 participants, of inorganic nitrate or beetroot juice. Systolic blood pressure fell 4.4 mmHg (95% CI 2.8 to 5.9); diastolic fell 1.1 mmHg but the confidence interval crossed zero, so that change was not significant. Beetroot juice produced the larger systolic effect. The trials were mostly short, blood pressure is a surrogate rather than a clinical event, and the review does not report a breakdown by sex, so how the effect divides between men and women is not established here.
This is a food effect, so the practical version is dietary rather than a supplement: a regular serving of beetroot or nitrate-rich leafy greens such as rocket, spinach or chard. Skipping antibacterial mouthwash matters too, since it removes the tongue bacteria the pathway depends on.
The study · 1
Siervo et al., inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults, a systematic review and meta-analysis · J Nutr 2013;143(6):818-826
Beetroot juice cut 24-hour blood pressure about 8/5 mmHg in hypertension
In people with high blood pressure, a daily glass of beetroot juice for four weeks lowered 24-hour blood pressure by about 8/5 mmHg and improved how well their arteries widened, compared with a beetroot juice that had the nitrate removed.
Kapil and colleagues randomized 68 hypertensive patients, 34 drug-naive and 34 already on treatment, to daily dietary nitrate as beetroot juice or a nitrate-depleted placebo juice for four weeks. Clinic blood pressure fell 7.7/2.4 mmHg, 24-hour ambulatory pressure 7.7/5.2 mmHg, and home pressure 8.1/3.8 mmHg; flow-mediated dilation improved by around 20% and pulse-wave velocity, a stiffness measure, fell 0.59 m/s. The placebo was the same juice with nitrate removed, so the comparison isolates the nitrate. It is one four-week trial, the abstract does not report the sex split, and the endpoints were pressure and vessel function rather than heart attacks or strokes.
The study · 1
Kapil et al., dietary nitrate provides sustained blood pressure lowering in hypertensive patients, a randomized, phase 2, double-blind, placebo-controlled study · Hypertension 2015;65(2):320-327
Flow-mediated dilation raised by exercise across randomized trials
Exercise improved how well arteries widen across pooled trials. Aerobic training raised flow-mediated dilation by about 2.8 percentage points, with resistance and combined training close behind, and harder aerobic training helped more.
Ashor and colleagues pooled randomized controlled trials of at least four weeks in adults, comparing exercise with non-exercise or sedentary controls, and measured flow-mediated dilation before and after. Every modality improved it: aerobic exercise by a weighted mean difference of 2.79 percentage points (95% CI 2.12 to 3.45), resistance training by 2.52 (95% CI 1.11 to 3.93), and combined training by 2.07 (95% CI 0.70 to 3.44). A dose-response relationship appeared for aerobic intensity, where a 2-MET rise in absolute intensity or a 10% rise in relative intensity gave roughly a 1% unit improvement in flow-mediated dilation, while for resistance training greater frequency mattered more than intensity. This complements the single small mechanistic study that isolated shear stress as the trigger: it gives the size of the training effect across many trials and both sexes, though flow-mediated dilation remains a marker of vascular function rather than a count of events.
Who this may not transfer to:Pooled from randomized trials across mixed populations; the review does not report a breakdown by sex, so how the same gain divides between men and women is not established here, and endothelial responses to training can differ by sex, age and fitness.
The study · 1
Ashor et al., exercise modalities and endothelial function, a systematic review and dose-response meta-analysis of randomized controlled trials · Sports Med 2015;45(2):279-296
L-arginine pills did not help the arteries after a heart attack
Taking L-arginine, the amino acid the body turns into nitric oxide, after a heart attack did not help arteries or heart function, and more people taking it died. Flooding the body with the raw material is not the same as the vessel making nitric oxide when it needs to.
The VINTAGE MI trial randomized 153 people after a heart attack, 104 of them men, mean age 60, to L-arginine or placebo on top of standard treatment. There was no improvement in ejection fraction or vascular stiffness. Six participants, 8.6%, in the L-arginine group died during the six-month study versus none on placebo (P=0.01), and the trial was stopped. The numbers are small and this is one specific population, but it is a pointed result: nitric oxide biology is about the right signal in the right place, and a constant oral supply of the precursor did not deliver a benefit and may have caused harm. It is the reason this page points to food nitrate and exercise rather than to an arginine supplement.
The study · 1
Schulman et al., L-arginine therapy in acute myocardial infarction, the VINTAGE MI randomized clinical trial · JAMA 2006;295(1):58-64
Three hours of sitting reduced how the leg artery widens
Sitting still for three hours made the artery in the leg less able to widen. Taking vitamin C first stopped that from happening, which suggests the problem is stillness letting damaging oxidation build up and use up nitric oxide.
Thosar and colleagues had 11 healthy young men, mean age about 24, sit for three hours while flow-mediated dilation was measured in the superficial femoral artery in the thigh. Function fell over the three hours. In a second arm, taking vitamin C beforehand prevented the decline at one, two and three hours (P=0.009, 0.016 and 0.004). Because vitamin C is an antioxidant, its protective effect implicates oxidative stress, which consumes nitric oxide, as the reason stillness impairs the vessel; when the legs are still, blood flow and the shear stress that drives eNOS both drop. It is a small, young, male sample and an acute measurement, so it demonstrates the mechanism rather than a long-term consequence.
Who this may not transfer to:Eleven young men. Vascular responses to sitting and to antioxidants may differ with sex, age and fitness, so this small study does not establish the same result in women or older adults.
The practical read is not to take vitamin C but to break up long sitting: standing or a short walk every half hour restores the blood flow that keeps the vessel lining working, which is the flow-based route rather than the antioxidant one.
The study · 1
Thosar et al., antioxidant vitamin C prevents decline in endothelial function during sitting · Med Sci Monit 2015;21:1015-1021
Progress Markers
Each 1% higher flow-mediated dilation, about 13% lower event risk
People whose arteries widen better have fewer future heart attacks and strokes: each 1% better flow-mediated dilation went with about 13% lower risk across 5,500 people. It is a good marker of risk, which is a different thing from showing that raising it prevents events.
Inaba and colleagues pooled 14 studies, 5,547 participants, and found that each 1% increase in brachial flow-mediated dilation was associated with a relative risk of future cardiovascular events of 0.87 (95% CI 0.83 to 0.91), about 13% lower risk per percentage point. This is why flow-mediated dilation is treated as a meaningful readout of vascular health. The inputs are observational cohorts, so the usual limits apply: better function travels with fewer risk factors, and a marker that predicts events is a surrogate, so it does not by itself establish that a treatment which raises it will lower events to the same degree.
The study · 1
Inaba et al., prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery, a meta-analysis · Int J Cardiovasc Imaging 2010;26(6):631-640
Exercise is the clearest lever, and the pathway has been isolated in a controlled test. When researchers trained people and then blunted the exercise-driven rise in blood flow, and so in shear stress, in one arm with a cuff, that arm did not improve while the free arm did. Pooling randomized trials, exercise of every kind raised flow-mediated dilation: aerobic training by about 2.8 percentage points, with resistance and combined training close behind, and harder aerobic training helped more.
Dietary nitrate is the second lever. Across sixteen trials, beetroot juice and other nitrate-rich foods lowered the top blood-pressure number by about 4 to 5 mmHg, on the scale of a single tablet. In people who already had high blood pressure, a daily glass of beetroot juice for four weeks lowered 24-hour pressure by about 8/5 mmHg and improved vessel function by roughly a fifth. It is a food effect, best had from food. The full food story sits on the dietary nitrate and beetroot page.
The losses are measured too. Three hours of unbroken sitting reduced how well the thigh artery could widen, because stillness lets blood flow and shear stress fall. And the lining makes less nitric oxide with age: in men flow-mediated dilation begins declining around 40, while in women it holds up until the early 50s, around menopause, then drops faster, a pattern that fits estrogen supporting eNOS until then.
That reading predicts risk. Across more than five thousand people, each 1% higher flow-mediated dilation went with about 13% lower risk of a future cardiovascular event. It tracks risk closely, which is not proof that raising it prevents events.
One popular shortcut does not work. L-arginine is the raw material eNOS uses, so more of it should mean more nitric oxide. In the trial that tested it, it did not.
After a heart attack, L-arginine supplements produced no improvement to the arteries or heart function, and the trial was stopped when six people taking them had died against none on placebo. Flooding the body with the raw material is not the same as the lining making nitric oxide at the right place and moment.
What This Means For You
None of this costs anything.
- Move often, and break up long sitting. Standing or a short walk every half hour restores the blood flow that keeps the lining working, and it is the flow, not a supplement, that raises nitric oxide.
- Exercise regularly. Aerobic training, resistance work and the two combined all raised how well vessels widen in trials, so the movement you will keep doing is the right one.
- Eat nitrate-rich vegetables. A regular serving of beetroot or leafy green vegetables such as rocket, spinach or chard feeds the food-nitrate route and lowers blood pressure a modest amount. It is a food effect, best had from food. A supplement does not reproduce it.
- Skip the L-arginine NO-booster pills. The precursor supplement did not deliver a benefit in the trial that tested it, and the money is better kept.
Go Deeper
This page describes the machinery. The pages that act on it, or depend on it:
- Dietary nitrate and beetroot, the food dose that works, who gains most, and why mouthwash switches it off.
- The oral microbiome, where the tongue bacteria that run the food-nitrate step live.
- Cardiovascular training and walking, the movement side of keeping the lining working.
- High blood pressure, where endothelial function, dietary nitrate and exercise all come together.
The Chinese Medicine View
Common Questions
What is nitric oxide, and what does it do?
In the blood vessels it is the main signal for widening them. The endothelium, the single cell layer lining every vessel, makes nitric oxide with the enzyme eNOS and releases it into the vessel wall, where it signals the muscle there to relax. A relaxed wall means a wider vessel, more flow and lower pressure. The gas lasts only seconds, so what matters is not a level you can store but how much your lining is making where and when it is needed.
Does beetroot really lower blood pressure?
Yes, modestly. Across sixteen trials, dietary nitrate lowered the top blood-pressure number by about 4 to 5 mmHg, and in people who already had high blood pressure, four weeks of daily beetroot juice lowered 24-hour pressure by roughly 8/5 mmHg and improved how well their vessels widened. It is on the scale of a single blood-pressure tablet. It works best as food, and antibacterial mouthwash blunts it by removing the tongue bacteria the pathway needs.
Do NO-booster supplements work?
The popular one, L-arginine, mostly does not. It is the raw material eNOS uses to make nitric oxide, so on paper more of it should mean more gas, but in the trial that tested it after a heart attack it produced no benefit to the arteries or heart function, and more people taking it died. Nitric oxide biology is about the right signal in the right place at the right moment, which food nitrate and movement provide and a steady oral dose does not.
Does sitting hurt my circulation?
Over a few hours, yes, and it is reversible. Three hours of unbroken sitting reduced how well the leg artery could widen, because when the legs are still, blood flow and the shear stress that drives the lining both fall. The fix is movement: standing or a short walk every half hour restores the flow that keeps the lining working. A supplement does not do it.
What is flow-mediated dilation?
It is the standard way to measure how well your vessel lining is working. A cuff blocks blood flow in the arm for a few minutes, and when it releases, the rush of returning blood widens the artery. How much it widens reflects how much nitric oxide the lining can make on demand. It matters because it tracks risk: across more than five thousand people, each 1% higher flow-mediated dilation went with about 13% lower risk of a future cardiovascular event.
Explore Related
Other pages this one connects to, by the evidence they share, the outcomes they touch, and the ground they cover.
Pages that lead here: Heat Exposure · Red & Near-Infrared Light
All 10 sources on this page independently checked and cross-referenced.
Thomas Dehli, Founder & Editor, Sacred Lotus
Sacred Lotus has published Chinese medicine reference material since 2001. Integrative pages are held to the same standard as the herb and formula library: cite the source, grade the claim at its real strength, and say where the research has not looked. This page is educational and it is not medical advice. Last reviewed and updated August 10, 2026.
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