Formulas for vascular health


Vessel Dynamics – Moving for vascular health


As explained in previous articles, vascular health depends on the endothelial lining of blood vessels. Physical activity may help prevent endothelial disease by increasing blood flow and shear stress, which stimulates production of beneficial nitric oxide (NO). In some cases, regular exercise may even be able to restore endothelial health in persons with heart disease, diabetes, or other chronic conditions.

Cardiovascular Disease

After 12 weeks of regular aerobic exercise, people with or without high blood pressure had increased blood vessel release of nitric oxide (NO), which signals the endothelium to relax blood vessels and increase blood flow.1

Exercise increases NO levels in the blood vessel wall by enhancing activity of an enzyme known as endothelial nitric oxide synthase (eNOS), which limits heart dysfunction and abnormal enlargement in patients with heart disease.2,3 Exercise training is therefore recommended to prevent and treat cardiovascular conditions.2

Aerobic exercise training at moderate intensity 3 days a week for 6 months improved blood flow, endothelial function and vascular health in pre- or post-menopausal African American women, who are known to be at increased risk for cardiovascular disease.4

Among patients with coronary artery disease, 6 months of aerobic exercise training performed at high frequency was more effective than low frequency training at increasing endothelial function.5

What’s even more exciting is that the improvements in endothelial function brought about by exercise and antioxidant intake are clinically meaningful. In patients with peripheral artery disease, these interventions may improve pain-free walking distance, allowing them to carry out more daily activities.6

High blood levels of homocysteine increase risk for coronary artery disease, but exercise may mitigate this risk by reducing oxidative injury and restoring endothelial function via its effects on NADPH oxidase.7

Another cardiovascular risk factor is high lipid levels. When boys exercised before high-fat meals, they had less endothelial dysfunction after eating than those who were inactive.8

Serious complications of cardiovascular disease which may respond to endothelial benefits of exercise include abdominal aortic aneurysm 9, heart transplantation10, cognitive impairment caused by small strokes11, and pre-eclampsia of pregnancy.12

Other Chronic Diseases

Exercise, alone or in combination with better diet or other interventions, appears to improve damaged endothelial function and physical fitness in type 213,14 and type 1 diabetes15, resulting in better control of blood sugar. High-intensity interval training appears to improve endothelial health as well as other metabolic and cardiovascular risk factors, particularly obesity, in patients with type 2 diabetes.16,17

When obese people exercise, their muscles release a protein known as irisin, which increases the diminished levels of circulating endothelial progenitor cells involved in restoring damaged endothelium 18. Aerobic exercise in obese or overweight adults not only improves endothelial function but also increases levels of VEGFA, which controls growth of new blood vessels, in subcutaneous fat.19

Even a single session of aerobic exercise may prevent reversible endothelial dysfunction associated with drinking sugar-sweetened beverages, which is a major culprit in the obesity epidemic.20 To help overweight children improve endothelial function, a video game involving dancing is highly effective.21

Cancer patients who exercise have increased numbers and improved function of natural killer (NK) cells, which appears to result from better endothelial function, shear stress, and NO signaling. NK cells are a type of immune cell linked to better cancer outcomes, including longer periods of being cancer-free.22

Inflammatory and autoimmune conditions in which exercise may help restore damaged endothelial function, thereby reducing symptoms, include rheumatoid arthritis.23

What If We Overdo It?

Like all good things, exercise can be overdone, potentially damaging the endothelium rather than healing it. This may occur in professional ballet dancers24 or endurance athletes. Highly trained cyclists may develop an arterial disease known as endofibrosis, with progressive thickening of the endothelial wall in a major leg artery. However, this rarely occurs before cycling a total of approximately 75,000 to 93,000 miles25, so most of us don’t have to worry.

Intense physical training could potentially damage the endothelium by using up antioxidants and increasing free radical production, thereby decreasing blood vessel relaxation controlled by endothelium.26

So the take-home lesson for most of us, whether in good health or dealing with chronic disease, is not to be a weekend warrior. Instead, we should engage in a regular program of moderate or even vigorous exercise, provided we allow time for our bodies to recover and adapt to the effects of shear stress. 27 Ask your doctor about which exercise prescription is right for you, and move on to vascular health!

+ References


  1. Higashi Y, Sasaki S, Kurisu S. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. Circulation. 1999;100:1194–1202
  2. Fernandes T, Gomes-Gatto CV, Pereira NP, Alayafi YR, das Neves VJ, Oliveira EM. NO signaling in the cardiovascular system and exercise. Adv Exp Med Biol. 2017;1000:211-245. doi: 10.1007/978-981-10-4304-8_13.
  3. Ballard KD, Duguid RM, Berry CW, Dey P, Bruno RS, Ward RM, Timmerman KL. Effects of prior aerobic exercise on sitting-induced vascular dysfunction in healthy men. Eur J Appl Physiol. 2017 Dec;117(12):2509-2518. doi: 10.1007/s00421-017-3738-2. Epub 2017 Oct 10.
  4. Grimm H, Kretzschmar JJ, Thakkar S, Ling C, Diaz KM, Sturgeon K, Feairheller DL, Perkins A, Lee H, Williamson S, Babitt D, Brown MD. Aerobic exercise effects on endothelial health status in pre- and post-menopausal African American women. http://hyper.ahajournals.org/content/62/Suppl_1/A302 Hypertension. 2013;62:A302
  5. Borges JP, Nascimento AR, Lopes GO, Medeiros-Lima DJM, Coelho MP, Nascimento PMC, Kopiler DA, Matsuura C, Mediano MFF, Tibirica E. The impact of exercise frequency upon microvascular endothelium function and oxidative stress among patients with coronary artery disease. Clin Physiol Funct Imaging. 2017 Dec 27. doi: 10.1111/cpf.12492. [Epub ahead of print].
  6. Gardner AW, Montgomery PS, Zhao YD, Ungvari Z, Csiszar A, Sonntag WE. Endothelial cell inflammation and antioxidant capacity are associated with 6-minute walk performance in patients with symptomatic peripheral artery disease. Angiology. 2017 Jan 1:3319717726934. doi: 10.1177/0003319717726934. [Epub ahead of print].
  7. Chan SH, Hung CH, Shih JY, Chu PM, Cheng YH, Lin HC, Hsieh PL, Tsai KL. Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling. Redox Biol. 2018 Apr;14:116-125. doi: 10.1016/j.redox.2017.08.016. Epub 2017 Aug 24.
  8. Sedgwick MJ, Morris JG, Nevill ME, Barrett LA. The accumulation of exercise and postprandial endothelial function in boys. Scand J Med Sci Sports. 2014 Feb;24(1):e11-9. doi: 10.1111/sms.12101. Epub 2013 Aug 15.
  9. Bailey TG, Perissiou M, Windsor M, Schulze K, Nam M, Magee R, Leicht AS, Green DJ, Greaves K, Golledge J, Askew CD. Effects of acute exercise on endothelial function in abdominal aortic aneurysm patients. Am J Physiol Heart Circ Physiol. 2017 Sep 22:ajpheart.00344.2017. doi: 10.1152/ajpheart.00344.2017. [Epub ahead of print].
  10. Yardley M, Ueland T, Aukrust P, Michelsen A, Bjørkelund E, Gullestad L, Nytrøen K. Immediate response in markers of inflammation and angiogenesis during exercise: a randomised cross-over study in heart transplant recipients. Open Heart. 2017 Nov 28;4(2):e000635. doi: 10.1136/openhrt-2017-000635. eCollection 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708310/
  11. Dao E, Hsiung GR, Liu-Ambrose T. The role of exercise in mitigating subcortical ischemic vascular cognitive impairment. Neurochem. 2017 Aug 21. doi: 10.1111/jnc.14153. [Epub ahead of print].
  12. Skow RJ, King EC, Steinback CD, Davenport MH. The influence of prenatal exercise and pre-eclampsia on maternal vascular function. Clin Sci (Lond). 2017 Aug 10;131(17):2223-2240. doi: 10.1042/CS20171036. Print 2017 Sep 1.
  13. Francois ME, Myette-Cote E, Bammert TD, Durrer C, Neudorf H, DeSouza CA, Little JP. Carbohydrate-restriction with postmeal walking effectively mitigates postprandial hyperglycemia and improves endothelial function in type 2 diabetes. Am J Physiol Heart Circ Physiol. 2017 Oct 13:ajpheart.00524.2017. [Epub ahead of print].
  14. Reusch JE, Bridenstine M, Regensteiner JG. Type 2 diabetes mellitus and exercise impairment. Rev Endocr Metab Disord. 2013 Mar;14(1):77-86. doi: 10.1007/s11154-012-9234-4.
  15. Hall B, Zebrowska A, Kaminski T, Stanula A, Robins A. Effects of hypoxia during continuous and intermittent exercise on glycaemic control and selected markers of vascular function in type 1 diabetes. [Article in German]. Exp Clin Endocrinol Diabetes. 2017 Sep 19. doi: 10.1055/s-0043-110482. [Epub ahead of print].
  16. Francois ME, Durrer C, Pistawka KJ, Halperin FA, Chang C, Little JP. Combined interval training and post-exercise nutrition in type 2 diabetes: a randomized control trial. Front Physiol. 2017 Jul 25;8:528. doi: 10.3389/fphys.2017.00528. eCollection 2017. PMID: 28790929. PMCID: PMC5524835.
  17. Chuensiri N, Suksom D, Tanaka H. Effects of high-intensity intermittent training on vascular function in obese preadolescent boys. Child Obes. 2017 Nov 3. doi: 10.1089/chi.2017.0024. [Epub ahead of print].
  18. Huang J, Wang S, Xu F, Wang D, Yin H, Lai Q, Liao J, Hou X, Hu M. Exercise training with dietary restriction enhances circulating irisin level associated with increasing endothelial progenitor cell number in obese adults: an intervention study. PeerJ. 2017 Aug 14;5:e3669. doi: 10.7717/peerj.3669. eCollection 2017.
  19. Van Pelt DW, Guth LM, Horowitz JF. Aerobic exercise elevates markers of angiogenesis and macrophage IL-6 gene expression in the subcutaneous adipose tissue of overweight-to-obese adults. J Appl Physiol (1985). 2017 Nov 1;123(5):1150-1159. Epub 2017 Aug 10. doi: 10.1152/japplphysiol.00614.2017.
  20. Varsamis P, Walther G, Share B, Taylor F, Stewart S, Lorenzen C, Loader J. Transient endothelial dysfunction induced by sugar-sweetened beverage consumption may be attenuated by a single bout of aerobic exercise. Microvasc Res. 2018 Jan;115:8-11. doi: 10.1016/j.mvr.2017.07.003. Epub 2017 Jul 31.
  21. Murphy EC, Carson L, Neal W, Baylis C, Donley D, Yeater R. Effects of an exercise intervention using Dance Dance Revolution on endothelial function and other risk factors in overweight children. Int J Pediatr Obes. 2009;4(4):205-14. doi: 10.3109/17477160902846187.
  22. Evans W. NK cell recruitment and exercise: Potential immunotherapeutic role of shear stress and endothelial health. https://doi.org/10.1016/j.mehy.2017.10.015 https://www.sciencedirect.com/science/article/pii/S0306987717308459 Volume 109, November 2017, Pages 170-173
  23. Metsios GS, Stavropoulos-Kalinoglou A, Veldhuijzen van Zanten JJ, Nightingale P, Sandoo A, Dimitroulas T, Kitas GD, Koutedakis Y. Individualised exercise improves endothelial function in patients with rheumatoid arthritis. Ann Rheum Dis. 2014 Apr;73(4):748-51. doi: 10.1136/annrheumdis-2013-203291. Epub 2013 Jul 31.
  24. Hoch AZ, Papanek P, Szabo A, Widlansky ME, Gutterman DD. Folic acid supplementation improves vascular function in professional dancers with endothelial dysfunction. PM R. 2011 Nov;3(11):1005-12. doi: 10.1016/j.pmrj.2011.02.014. Epub 2011 Jun 29.
  25. Abraham P, Saumet JL, Desvaux B, Fromy B. Exercise and endothelial function. Circulation. 2000;102:e168. https://doi.org/10.1161/01.CIR.102.20.e168
  26. Bergholm R, Mäkimattila S, Valkonen M, Liu ML, Lahdenperä S, Taskinen MR, Sovijärvi A, Malmberg P, Yki-Järvinen H. Intense physical training decreases circulating antioxidants and endothelium-dependent vasodilatation in vivo. Atherosclerosis. 1999 Aug;145(2):341-9.
  27. Dawson EA, Cable NT, Green DJ, Thijssen DH. Do acute effects of exercise on vascular function predict adaptation to training? Eur J Appl Physiol. 2017 Dec 12. doi: 10.1007/s00421-017-3724-8. [Epub ahead of print]

About the author:

Laurie Barclay, MD

Laurie Barclay, MD, is a neurologist who has published more than 60 peer-reviewed journal articles concerning her research on Alzheimer’s disease and other dementias. She is editor and author of several chapters in “Clinical Geriatric Neurology,” a medical textbook which has been translated into Italian and has also written many other medical book chapters both for physicians and for the lay public. She has been an invited speaker on her own research and on other topics at medical and scientific meetings and lectures worldwide.

Dr. Barclay received her BA from Princeton University in 1974 and her medical degree from Cornell in 1978. Her training includes a medical internship and neurology residency at the New York Hospital-Cornell, and a fellowship in neurobiology at the Burke Rehabilitation Center-Cornell, where she also served as chief of the spinal cord trauma unit and clinical director of dementia research. After being an assistant professor of neurology at the New York Hospital-Cornell from 1983 to 1987 and at the University of South Florida from 1987 to 1992, she went into private practice and medico-legal consulting.

Dr. Barclay is board-certified in neurology by the American Board of Psychiatry and Neurology, in forensic medicine by the American Board of Forensic Medicine, and in traumatic stress by the American Academy of Experts in Traumatic Stress. In addition to being an associate in the American Academy of Neurology and in the World Federation of Neurology Research Group on Dementia, she is a member of the American Medical Writers Association, the American Medical Association, and the American Association for the Advancement of Science. Her many awards include 1993 Woman of the Year and listings in “Who’s Who in the World” and in other “Who’s Who” directories.

While freelance writing for WebMD, Dr. Barclay is also Senior Medical Editor for the “Medical Disability Advisor,” and is writing a memoir about her life as an amateur ballroom dance champion with her husband and partner, Richard Collett.


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