What Is Endothelial Dysfunction?

Narrowing of the blood vessels that can cause chest pain

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Endothelial dysfunction is a narrowing of blood vessels due to their inner lining (endothelium) not producing enough of the gas that normally keeps them open. This is a form of coronary artery disease (CAD), but does not involve a blockage inside the artery.

The constricting of the vessels causes chronic chest pain (angina) and can lead to more serious cardiovascular conditions, including heart attack and stroke. Fortunately, endothelial dysfunction is often reversible.

Lifestyle changes, including weight loss, diet, and cardiovascular exercise, are often enough to undo the damage. Cholesterol-lowering drugs known as statins can also treat the condition.

This article discusses endothelial dysfunction, including its symptoms and causes. It also covers how endothelial dysfunction is diagnosed and treated.

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Function of the Endothelial Layer

In the body's arterioles (the small arteries that precisely regulate the flow of blood to the tissues), the endothelial layer (or endothelium) is the inner lining of cells. The layer has several critical functions in the body.

The endothelium maintains the proper dilation and constriction of the blood vessels. This function determines how much blood is received by the body's various tissues on a moment-to-moment basis.

Endothelial "tone" (the balance between dilation and constriction) also largely determines a person’s blood pressure, and how much work the heart must do to pump blood out to the body. 

In addition, the endothelium also protects the tissues from various toxic substances, regulates the blood clotting mechanism controls fluid, electrolytes, and numerous other substances that pass back and forth between the blood and the tissues, and regulates inflammation in the tissues.

The proper functioning of the endothelium is critical for the normal function of the body’s tissues and organs.

When the endothelial layer fails to perform all these functions adequately—in other words, when endothelial dysfunction is present—conditions will favor the development of atherosclerosis, hypertension, and other types of cardiovascular disease. 

Causes of Endothelial Dysfunction

Endothelial dysfunction is related to a reduction in nitric oxide (NO) levels in blood vessel walls.

NO is a gas that is produced by the metabolism of the amino acid L-arginine. It acts locally within blood vessels to help modulate vascular tone and other important endothelial duties.

Certain health conditions—including diabetes, high blood pressure, and heart failure—can limit how much NO the blood vessels make or affect how the body uses the NO that is made. It's thought that high blood sugar levels in diabetes, for example, can have a negative effect on NO levels.

Lifestyle habits can also contribute to lower levels of NO. For instance, some studies have shown that people who smoke cigarettes exhale less NO than non-smokers.

A deficiency in nitric oxide production leads or contributes to:

  • Excess constriction of blood vessels (which can produce hypertension)
  • Activation of platelets (leading to blood clotting)
  • Stimulation of inflammation in blood vessel walls (which contributes to atherosclerosis)
  • Permeability of the vessel walls to damaging lipoproteins and various toxins

The resulting abnormalities in blood vessel function tend to promote cardiovascular disease. 

In addition, endothelial dysfunction can directly cause abnormal constriction of the small arteries and is thought to be a significant factor in cardiac syndrome X (CSX) and, potentially, diastolic dysfunction.

Factors Associated With Endothelial Dysfunction

The precise pathways by which a person develops endothelial dysfunction are still being worked out. However, it seems clear that numerous medical disorders, habits, and unavoidable life events can contribute to it, including:

Additionally, endothelial dysfunction is more common in those born female vs. male.

Signs and Symptoms of Endothelial Dysfunction

The main symptom of endothelial dysfunction is chest pain. Some people also feel shortness of breath.

People often find that the chest pain is worse when they are physically active or experiencing emotional stress. 

The pain can also come on during other times when the body is under stress—for example, during a person’s monthly menstrual period.

How Endothelial Dysfunction Is Diagnosed

Making a formal diagnosis of endothelial dysfunction is usually not necessary. Some degree of endothelial dysfunction can be safely assumed in any person who has CAD, hypertension, or major risk factors for heart disease. However, actually measuring a patient's endothelial function is not something providers routinely do.

If endothelial dysfunction is suspected but without a clear reason for it, the diagnosis can be confirmed with tests that measure the ability of the blood vessels to dilate (during catheterization or with ultrasound) in response to the administration of acetylcholine.

Treatment for Endothelial Dysfunction

Treatment for endothelial function can include weight loss, exercise, smoking cessation, controlling hypertension, and managing conditions like diabetes.

Some people find that lifestyle changes alone help, while others feel better when they also take medication.

Examples of things you can do to manage endothelial dysfunction include:

  • Creating a nutritious eating plan that supports your health and weight goals
  • Finding exercise or physical activity that you enjoy and can do regularly
  • Quitting smoking or using substances
  • Limiting alcohol and caffeine
  • Reaching out for support in managing your stress levels (for example, working with a mental health provider)

If your provider thinks medication would be beneficial for you in managing endothelial dysfunction, they might prescribe you:

Other drugs that have shown promise include estrogen, ranolazine, L-arginine, and sildenafil. Your provider might recommend you for experimental therapies to treat endothelial function—for example, taking part in a clinical trial to test a new medication. 

There has been some research on external counter pulsation (ECP) therapy to help with angina and other heart conditions when other treatments have not worked.

With this, you are hooked up to an EKG to watch your heart rate and have blood pressure cuffs put on your arms and legs. They are inflated and deflated based on your heart rate. This process helps make sure that the blood that goes to your heart has more oxygen in it.

You will need to do this treatment daily for several weeks or even a few months, so it can be very time-consuming. Each session takes about an hour and you will have to go to your provider’s office, clinic, or hospital to have it done.

You can ask your provider if they think it would be worth trying ECP for your endothelial dysfunction. 


Endothelial dysfunction is a type of coronary artery disease (CAD) that causes chest pain. It happens because the vessels in the heart get too narrow. 

Over time, people who have endothelial dysfunction can develop more serious heart conditions. Making lifestyle changes and taking medications can help manage the condition and may even reverse it.

A Word From Verywell

In recent years, medical researchers have found that endothelial dysfunction is an important underlying contributor to many cardiovascular problems.

That said, heart-healthy habits like getting regular exercise, eating a nutritious diet, watching your stress, quitting smoking, and managing any chronic health conditions like high blood pressure and diabetes can also help treat or even prevent endothelial dysfunction.

13 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Taqueti VR, Di Carli MF. Coronary microvascular disease pathogenic mechanisms and therapeutic options: JACC state-of-the-art review. J Am Coll Cardiol. 2018;72:2625. doi:10.1016/j.jacc.2018.09.042

  2. Cyr AR, Huckaby LV, Shiva SS, Zuckerbraun BS. Nitric oxide and endothelial dysfunctionCrit Care Clin. 2020;36(2):307-321. doi:10.1016/j.ccc.2019.12.009

  3. Wang M, Li Y, Li S, Lv J. Endothelial dysfunction and diabetic xardiomyopathyFrontiers in Endocrinology. 2022;13. doi:10.3389/fendo.2022.851941

  4. Michael Pittilo R. Cigarette smoking, endothelial injury and cardiovascular diseaseInt J Exp Pathol. 2000;81(4):219-230. doi:10.1046/j.1365-2613.2000.00162.x

  5. Malinovschi A. Effect of smoking on exhaled nitric oxide and flow-independent nitric oxide exchange parametersEuropean Respiratory Journal. 2006;28(2):339-345. doi:10.1183/09031936.06.00113705

  6. Modena MG, Bonetti L, Coppi F, Bursi F, Rossi R. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol. 2002;40:505. doi:10.1016/s0735-1097(02)01976-9

  7. Stanford Medicine. Symptoms of endothelial dysfunction.

  8. Yeboah J, Folsom AR, Burke GL, et al. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation 2009; 120:502. DOI:10.1161/CIRCULATIONAHA.109.86480

  9. Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL. Ischemia and no obstructive coronary artery disease (INOCA): Developing evidence-based therapies and research agenda for the next decade. Circulation. 2017;135:1075. doi:10.1161/CIRCULATIONAHA.116.024534

  10. Cedars-Sinai. Endothelial function testing.

  11. Beck DT, Martin JS, Casey DP, Avery JC, Sardina PD, Braith RW. Enhanced external counterpulsation improves endothelial function and exercise capacity in patients with ischaemic left ventricular dysfunctionClin Exp Pharmacol Physiol. 2014;41(9):628-636. doi:10.1111/1440-1681.12263

  12. Cedars-Sinai. External counter pulsation.

  13. University of Michigan Health. EECP treatment.

By Richard N. Fogoros, MD
Richard N. Fogoros, MD, is a retired professor of medicine and board-certified in internal medicine, clinical cardiology, and clinical electrophysiology.