European Journal of Applied Physiology

, Volume 113, Issue 2, pp 519–528 | Cite as

Exercise and diet-induced weight loss attenuates oxidative stress related-coronary vasoconstriction in obese adolescents

  • Zhaohui Gao
  • Marsha Novick
  • Matthew D. Muller
  • Ronald J. Williams
  • Samson Spilk
  • Urs A. Leuenberger
  • Lawrence I. Sinoway
Original Article


Obesity is a disease of oxidative stress (OS). Acute hyperoxia (breathing 100 % O2) can evoke coronary vasoconstriction by the oxidative quenching of nitric oxide (NO). To examine if weight loss would alter the hyperoxia-related coronary constriction seen in obese adolescents, we measured the coronary blood flow velocity (CBV) response to hyperoxia using transthoracic Doppler echocardiography before and after a 4-week diet and exercise regimen in 6 obese male adolescents (age 13–17 years, BMI 36.5 ± 2.3 kg/m2). Six controls of similar age and BMI were also studied. The intervention group lost 9 ± 1 % body weight, which was associated with a reduced resting heart rate (HR), reduced diastolic blood pressure (BP), and reduced RPP (all P < 0.05). Before weight loss, hyperoxia reduced CBV by 33 ± 3 %. After weight loss, CBV only fell by 15 ± 3 % (P < 0.05). In the control group, CBV responses to hyperoxia were unchanged during the two trials. Thus weight loss: (1) reduces HR, BP, and RPP; and (2) attenuates the OS-related coronary constrictor response seen in obese adolescents. We postulate that: (1) the high RPP before weight loss led to higher myocardial O2 consumption, higher coronary flow and greater NO production, and in turn a large constrictor response to hyperoxia; and (2) weight loss decreased myocardial oxygen demand and NO levels. Under these circumstances, hyperoxia-induced vasoconstriction was attenuated.


Obesity Weight loss Coronary circulation 



We are thankful to Cheryl Blaha and Jessica Mast for their expert study coordination and invaluable technical assistance during the studies. The authors also express gratitude to Dr. Stephen E. Cyran and Jennie Stoner for consulting assistance and outstanding secretarial skills. Supported by R01 HL070222 (L.S.), M01 RR010732 (GCRC Grant), C06 RR016499 (Construction Grant) from the National Institutes of Health (L.S.) and in part, under a grant with the Pennsylvania Department of Health using Tobacco Settlement Funds (L.S.). The Department specifically disclaims responsibility for any analyses, interpretations or conclusions.


  1. Abel ED, Litwin SE, Sweeney G (2008) Cardiac remodeling in obesity. Physiol Rev 88:389–419PubMedCrossRefGoogle Scholar
  2. Alpert MA, Lambert CR, Panayiotou H, Terry BE, Cohen MV, Massey CV, Hashimi MW, Mukerji V (1995a) Relation of duration of morbid obesity to left ventricular mass, systolic function, and diastolic filling, and effect of weight loss. Am J Cardiol 76:1194–1197PubMedCrossRefGoogle Scholar
  3. Alpert MA, Lambert CR, Terry BE, Cohen MV, Mulekar M, Massey CV, Hashimi MW, Panayiotou H, Mukerji V (1995b) Effect of weight loss on left ventricular diastolic filling in morbid obesity. Am J Cardiol 76:1198–1201PubMedCrossRefGoogle Scholar
  4. Ashrafian H, le Roux CW, Darzi A, Athanasiou T (2008) Effects of bariatric surgery on cardiovascular function. Circulation 118:2091–2102PubMedCrossRefGoogle Scholar
  5. Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA (1998) Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. New Engl J Med 338:1650–1656PubMedCrossRefGoogle Scholar
  6. Blumenthal JA, Sherwood A, Gullette EC, Babyak M, Waugh R, Georgiades A, Craighead LW, Tweedy D, Feinglos M, Appelbaum M, Hayano J, Hinderliter A (2000) Exercise and weight loss reduce blood pressure in men and women with mild hypertension: effects on cardiovascular, metabolic, and hemodynamic functioning. Arch Intern Med 160:1947–1958PubMedCrossRefGoogle Scholar
  7. Brook RD, Bard RL, Glazewski L, Kehrer C, Bodary PF, Eitzman DL, Rajagopalan S (2004) Effect of short-term weight loss on the metabolic syndrome and conduit vascular endothelial function in overweight adults. Am J Cardiol 93:1012–1016PubMedCrossRefGoogle Scholar
  8. Davi G, Guagnano MT, Ciabattoni G, Basili S, Falco A, Marinopiccoli M, Nutini M, Sensi S, Patrono C (2002) Platelet activation in obese women: role of inflammation and oxidant stress. JAMA J Am Med Assoc 288:2008–2014CrossRefGoogle Scholar
  9. Devereux RB, Reichek N (1977) Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation 55:613–618PubMedCrossRefGoogle Scholar
  10. Di Bello V, Santini F, Di Cori A, Pucci A, Talini E, Palagi C, Delle Donne MG, Marsili A, Fierabracci P, Valeriano R, Scartabelli G, Giannetti M, Anselmino M, Pinchera A, Mariani M (2008) Effects of bariatric surgery on early myocardial alterations in adult severely obese subjects. Cardiology 109:241–248PubMedCrossRefGoogle Scholar
  11. Duffy SJ, Castle SF, Harper RW, Meredith IT (1999) Contribution of vasodilator prostanoids and nitric oxide to resting flow, metabolic vasodilation, and flow-mediated dilation in human coronary circulation. Circulation 100:1951–1957PubMedCrossRefGoogle Scholar
  12. Duncker DJ, Bache RJ (2008) Regulation of coronary blood flow during exercise. Physiol Rev 88:1009–1086PubMedCrossRefGoogle Scholar
  13. Eckel RH, Krauss RM (1998) American Heart Association call to action: obesity as a major risk factor for coronary heart disease. AHA Nutrition Committee. Circulation 97:2099–2100PubMedCrossRefGoogle Scholar
  14. Eisenmann JC, Wickel EE, Welk GJ, Blair SN (2005) Relationship between adolescent fitness and fatness and cardiovascular disease risk factors in adulthood: the Aerobics Center Longitudinal Study (ACLS). Am Heart J 149:46–53PubMedCrossRefGoogle Scholar
  15. Feigl EO (1983) Coronary physiology. Physiol Rev 63:1–205PubMedGoogle Scholar
  16. Frisbee JC, Krishna UM, Falck JR, Lombard JH (2001) Role of prostanoids and 20-HETE in mediating oxygen-induced constriction of skeletal muscle resistance arteries. Microvasc Res 62:271–283PubMedCrossRefGoogle Scholar
  17. Gao Z, Spilk S, Momen A, Muller MD, Leuenberger UA, Sinoway LI (2012a) Vitamin C prevents hyperoxia-mediated coronary vasoconstriction and impairment of myocardial function in healthy subjects. Eur J Appl Physiol 112:483–492PubMedCrossRefGoogle Scholar
  18. Gao Z, Wilson TE, Drew RC, Ettinger J, Monahan KD (2012b) Altered coronary vascular control during cold stress in healthy older adults. Am J Physiol Heart Circ Physiol 302:H312–H318PubMedCrossRefGoogle Scholar
  19. Gately PJ, Cooke CB, Barth JH, Bewick BM, Radley D, Hill AJ (2005) Children’s residential weight-loss programs can work: a prospective cohort study of short-term outcomes for overweight and obese children. Pediatrics 116:73–77PubMedCrossRefGoogle Scholar
  20. Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Chayama K, Oshima T (2001) Effect of obesity on endothelium-dependent, nitric oxide-mediated vasodilation in normotensive individuals and patients with essential hypertension. Am J Hypertens 14:1038–1045PubMedCrossRefGoogle Scholar
  21. Higdon JV, Frei B (2003) Obesity and oxidative stress: a direct link to CVD? Arterioscler Thromb Vasc Biol 23:365–367PubMedCrossRefGoogle Scholar
  22. Keaney JF Jr, Larson MG, Vasan RS, Wilson PW, Lipinska I, Corey D, Massaro JM, Sutherland P, Vita JA, Benjamin EJ (2003) Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol 23:434–439PubMedCrossRefGoogle Scholar
  23. Khan NI, Naz L, Yasmeen G (2006) Obesity: an independent risk factor for systemic oxidative stress. Pak J Pharm Sci 19:62–65PubMedGoogle Scholar
  24. Kingwell BA, Sherrard B, Jennings GL, Dart AM (1997) Four weeks of cycle training increases basal production of nitric oxide from the forearm. Am J Physiol Heart Circ Physiol 272:H1070–H1077Google Scholar
  25. Laffer CL, Laniado-Schwartzman M, Nasjletti A, Elijovich F (2004) 20-HETE and circulating insulin in essential hypertension with obesity. Hypertension 43:388–392PubMedCrossRefGoogle Scholar
  26. Lee PJ, Choi AM (2003) Pathways of cell signaling in hyperoxia. Free Radic Biol Med 35:341–350PubMedCrossRefGoogle Scholar
  27. Lopes HF, Martin KL, Nashar K, Morrow JD, Goodfriend TL, Egan BM (2003) DASH diet lowers blood pressure and lipid-induced oxidative stress in obesity. Hypertension 41:422–430PubMedCrossRefGoogle Scholar
  28. Magarey AM, Daniels LA, Boulton TJ, Cockington RA (2003) Predicting obesity in early adulthood from childhood and parental obesity. Int J Obes Relat Metab Disord 27:505–513PubMedCrossRefGoogle Scholar
  29. Martorell R, Kettel Khan L, Hughes ML, Grummer-Strawn LM (2000) Overweight and obesity in preschool children from developing countries. Int J Obes Relat Metab Disord 24:959–967PubMedCrossRefGoogle Scholar
  30. McGill HC Jr, McMahan CA, Herderick EE, Zieske AW, Malcom GT, Tracy RE, Strong JP (2002) Obesity accelerates the progression of coronary atherosclerosis in young men. Circulation 105:2712–2718PubMedCrossRefGoogle Scholar
  31. McNulty PH, King N, Scott S, Hartman G, McCann J, Kozak M, Chambers CE, Demers LM, Sinoway LI (2005) Effects of supplemental oxygen administration on coronary blood flow in patients undergoing cardiac catheterization. Am J Physiol Heart Circ Physiol 288:H1057–H1062PubMedCrossRefGoogle Scholar
  32. Miyata N, Roman RJ (2005) Role of 20-hydroxyeicosatetraenoic acid (20-HETE) in vascular system. J Smooth Muscle Res 41:175–193PubMedCrossRefGoogle Scholar
  33. Momen A, Gahremanpour A, Mansoor A, Kunselman A, Blaha C, Pae W, Leuenberger UA, Sinoway LI (2007) Vasoconstriction seen in coronary bypass grafts during handgrip in humans. J Appl Physiol 102:735–739PubMedCrossRefGoogle Scholar
  34. Momen A, Mascarenhas V, Gahremanpour A, Gao Z, Moradkhan R, Kunselman A, Boehmer J, Sinoway LI, Leuenberger UA (2009) Coronary blood flow responses to physiological stress in humans. Am J Physiol Heart Circ Physiol 296:H854–H861PubMedCrossRefGoogle Scholar
  35. Muller MD, Gao Z, Drew RC, Herr MD, Leuenberger UA, Sinoway LI (2011) Effect of cold air inhalation and isometric exercise on coronary blood flow and myocardial function in humans. J Appl Physiol 111:1694–1702PubMedCrossRefGoogle Scholar
  36. Ogden CL, Carroll MD (2010) Prevalence of overweight, obesity, and extreme obesity among adults: United States, trends 1960–1962 through 2007–2008. National Center for Health Statistics. CDC.
  37. Pahkala K, Heinonen OJ, Lagstrom H, Hakala P, Simell O, Viikari JS, Ronnemaa T, Hernelahti M, Sillanmaki L, Raitakari OT (2008) Vascular endothelial function and leisure-time physical activity in adolescents. Circulation 118:2353–2359PubMedCrossRefGoogle Scholar
  38. Pasanisi F, Contaldo F, de Simone G, Mancini M (2001) Benefits of sustained moderate weight loss in obesity. Nutr Metab Cardiovasc Dis 11:401–406PubMedGoogle Scholar
  39. Quyyumi AA, Dakak N, Andrews NP, Gilligan DM, Panza JA, Cannon RO 3rd (1995) Contribution of nitric oxide to metabolic coronary vasodilation in the human heart. Circulation 92:320–326PubMedCrossRefGoogle Scholar
  40. Raitakari M, Ilvonen T, Ahotupa M, Lehtimaki T, Harmoinen A, Suominen P, Elo J, Hartiala J, Raitakari OT (2004) Weight reduction with very-low-caloric diet and endothelial function in overweight adults: role of plasma glucose. Arterioscler Thromb Vasc Biol 24:124–128PubMedCrossRefGoogle Scholar
  41. Roberts CK, Vaziri ND, Wang XQ, Barnard RJ (2000) Enhanced NO inactivation and hypertension induced by a high-fat, refined-carbohydrate diet. Hypertension 36:423–429PubMedCrossRefGoogle Scholar
  42. Roberts CK, Vaziri ND, Barnard RJ (2002) Effect of diet and exercise intervention on blood pressure, insulin, oxidative stress, and nitric oxide availability. Circulation 106:2530–2532PubMedCrossRefGoogle Scholar
  43. Rossner S, Hammarstrand M, Hemmingsson E, Neovius M, Johansson K (2008) Long-term weight loss and weight-loss maintenance strategies. Obes Rev 9:624–630PubMedCrossRefGoogle Scholar
  44. Schonfeld-Warden N, Warden CH (1997) Pediatric obesity. An overview of etiology and treatment. Pediatr Clin North Am 44:339–361PubMedCrossRefGoogle Scholar
  45. Singhal A (2005) Endothelial dysfunction: role in obesity-related disorders and the early origins of CVD. Proc Nutr Soc 64:15–22PubMedCrossRefGoogle Scholar
  46. Steinberger J, Daniels SR (2003) Obesity, insulin resistance, diabetes, and cardiovascular risk in children: an American Heart Association scientific statement from the Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young) and the Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism). Circulation 107:1448–1453PubMedCrossRefGoogle Scholar
  47. Strauss RS, Pollack HA (2001) Epidemic increase in childhood overweight, 1986–1998. JAMA J Am Med Assoc 286:2845–2848CrossRefGoogle Scholar
  48. Sundell J (2005) Obesity and diabetes as risk factors for coronary artery disease: from the epidemiological aspect to the initial vascular mechanisms. Diabetes Obes Metab 7:9–20PubMedCrossRefGoogle Scholar
  49. Teichholz LE, Kreulen T, Herman MV, Gorlin R (1976) Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol 37:7–11PubMedCrossRefGoogle Scholar
  50. Tounian P, Aggoun Y, Dubern B, Varille V, Guy-Grand B, Sidi D, Girardet JP, Bonnet D (2001) Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet 358:1400–1404PubMedCrossRefGoogle Scholar
  51. Vincent HK, Innes KE, Vincent KR (2007) Oxidative stress and potential interventions to reduce oxidative stress in overweight and obesity. Diabetes Obes Metab 9:813–839PubMedCrossRefGoogle Scholar
  52. Willens HJ, Chakko SC, Byers P, Chirinos JA, Labrador E, Castrillon JC, Lowery MH (2005) Effects of weight loss after gastric bypass on right and left ventricular function assessed by tissue Doppler imaging. Am J Cardiol 95:1521–1524PubMedCrossRefGoogle Scholar
  53. Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS, Lam CW, Metreweli C, Celermajer DS (2004) Effects of diet and exercise on obesity-related vascular dysfunction in children. Circulation 109:1981–1986PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Zhaohui Gao
    • 1
  • Marsha Novick
    • 2
  • Matthew D. Muller
    • 1
  • Ronald J. Williams
    • 2
  • Samson Spilk
    • 1
  • Urs A. Leuenberger
    • 1
  • Lawrence I. Sinoway
    • 1
    • 3
  1. 1.Penn State Hershey Heart and Vascular InstituteThe Milton S. Hershey Medical Center, The Pennsylvania State University College of MedicineHersheyUSA
  2. 2.Penn State Children’s HospitalThe Milton S. Hershey Medical Center, The Pennsylvania State University College of MedicineHersheyUSA
  3. 3.Department of Medicine, H047The Milton S. Hershey Medical Center, The Pennsylvania State University College of MedicineHersheyUSA

Personalised recommendations