Abstract
Endothelium is essential for maintenance of health of the vessel wall and for the local regulation of vascular tone and structure and haemostasis. Regular physical exercise, which is known to promote a favourable cardiovascular state, may improve endothelial function via several mechanisms. Indeed, it augments blood flow and laminar shear stress, resulting in increased nitric oxide production and bioavailability. In this regard, the beneficial effects of training on endothelial function can be mediated in a number of ways, including synthesis of molecular mediators, changes in neurohormonal release and oxidant/antioxidant balance. On the other hand, physical exercise can also elicit systemic molecular pathways connected with angiogenesis and chronic anti-inflammatory action with consequent modification of the endothelial function. However, its benefit depends on the type and intensity of training performed. While strenuous exercise increases oxidative metabolism and produces a pro-oxidant environment, only regular moderate physical activity promotes an antioxidant state and preserves endothelial function. Thus, exercise may have a beneficial effect on the development of cardiovascular disease through preserving endothelial function.
Similar content being viewed by others
References
Maldonado J, Pereira T, Polonia J, et al. Modulation of arterial stiffness with intensive competitive training. Rev Port Cardiol 2006; 25 (7-8): 709–14
Ehsani AA, Heath GW, Hagberg JM, et al. Effects of 12 months of intense exercise training on ischemicST-segment depression in patients with coronary arterydisease. Circulation 1981; 64 (6): 1116–24
Schuler G, Hambrecht R, Schlierf G, et al. Myocardial perfusion and regression of coronary artery disease inpatients on a regimen of intensive physical exercise andlow fat diet. J Am Coll Cardiol 1992; 19 (1): 34–42
Paterick TE, Fletcher GF. Endothelial function and cardiovascular prevention: role of blood lipids, exercise, andother risk factors. Cardiol Rev 2001; 9 (5): 282–6
Shephard RJ, Balady GJ. Exercise as cardiovascular therapy. Circulation 1999; 99 (7): 963–72
Lewis TV, Dart AM, Chin-Dusting JP, et al. Exercise training increases basal nitric oxide production from the forearm in hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 1999; 19 (11): 2782–7
Panza JA, Quyyumi AA, Brush Jr JE, et al. Abnormal endothelium-dependent vascular relaxation in patientswith essential hypertension. N Engl J Med 1990; 323 (1): 22–7
Taddei S, Virdis A, Mattei P, et al. Vasodilation to acetylcholine in primary and secondary forms of humanhypertension. Hypertension 1993; 21 (6 Pt 2): 929–33
Blair SN, Kohl 3rd HW, Barlow CE, et al. Changes in physical fitness and all-cause mortality: a prospectivestudy of healthy and unhealthy men. JAMA 1995; 273 (14): 1093–8
Tanaka H, Dinenno FA, Monahan KD, et al. Aging, habitual exercise, and dynamic arterial compliance. Circulation 2000; 102 (11): 1270–5
Giada F, Biffi A, Agostoni P, et al. Exercise prescription for the prevention and treatment of cardiovascular diseases:part I. J Cardiovasc Med (Hagerstown) 2008; 9 (5): 529–44
Davis PG, Bartoli WP, Durstine JL. Effects of acute exercise intensity on plasma lipids and apolipoproteins intrained runners. J Appl Physiol 1992; 72 (3): 914–9
Gaesser GA, Rich RG. Effects of high- and low-intensity exercise training on aerobic capacity and blood lipids. Med Sci Sports Exerc 1984; 16 (3): 269–74
Gaesser GA, Wilson LA. Effects of continuous and interval training on the parameters of the power-endurance timerelationship for high-intensity exercise. Int J Sports Med 1988; 9 (6): 417–21
Grediagin A, Cody M, Rupp J, et al. Exercise intensity does not effect body composition change in untrained, moderatelyoverfat women. J Am Diet Assoc 1995; 95 (6): 661–5
Haram PM, Kemi OJ, Wisloff U. Adaptation of endothelium to exercise training: insights from experimentalstudies. Front Biosci 2008; 13: 336–46
Verma S, Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation 2002; 105 (5): 546–9
Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362 (6423): 801–9
Franzoni F, Galetta F, Morizzo C, et al. Effects of age and physical fitness on microcirculatory function. Clin Sci (Lond) 2004; 106 (3): 329–35
Davies PF. Flow-mediated endothelial mechanotransduction. Physiol Rev 1995; 75 (3): 519–60
Davies PF, Spaan JA, Krams R. Shear stress biology of the endothelium. Ann Biomed Eng 2005; 33 (12): 1714–8
Noris M, Morigi M, Donadelli R, et al. Nitric oxide synthesis by cultured endothelial cells is modulated byflow conditions. Circ Res 1995; 76 (4): 536–43
Resnick N, Yahav H, Shay-Salit A, et al. Fluid shear stress and the vascular endothelium: for better and for worse. Prog Biophys Mol Biol 2003; 81 (3): 177–99
Tao J, Yang Z, Wang JM, et al. Shear stress increases Cu/Zn SOD activity and mRNA expression in humanendothelial progenitor cells. J Hum Hypertens 2007; 21 (5): 353–8
Paravicini TM, Touyz RM. Redox signaling in hypertension. Cardiovasc Res 2006; 71 (2): 247–58
Palmer RM, Rees DD, Ashton DS, et al. L-arginine is the physiological precursor for the formation of nitric oxidein endothelium-dependent relaxation. Biochem Biophys Res Commun 1988; 153 (3): 1251–6
Wang J, Wolin MS, Hintze TH. Chronic exercise enhances endothelium-mediated dilation of epicardial coronaryartery in conscious dogs. Circ Res 1993; 73 (5): 829–38
Miller VM, Vanhoutte PM. Enhanced release of endothelium-derived factor(s) by chronic increases inblood flow. Am J Physiol 1988; 255 (3 Pt 2): H446–51
Tsao PS, Lewis NP, Alpert S, et al. Exposure to shear stress alters endothelial adhesiveness: role of nitric oxide. Circulation 1995; 92 (12): 3513–9
Tsao PS, Buitrago R, Chan JR, et al. Fluid flow inhibits endothelial adhesiveness: nitric oxide and transcriptionalregulation of VCAM-1. Circulation 1996; 94 (7): 1682–9
Niebauer J, Cooke JP. Cardiovascular effects of exercise: role of endothelial shear stress. J Am Coll Cardiol 1996; 28 (7): 1652–60
Green DJ, Maiorana A, O’Driscoll G, et al. Effect of exercise training on endothelium-derived nitric oxidefunction in humans. J Physiol 2004; 561 (Pt 1): 1–25
Kamiya A, Togawa T. Adaptive regulation of wall shear stress to flow change in the canine carotid artery. Am JPhysiol 1980; 239 (1): H14–21
Langille BL, O’Donnell F. Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 1986; 231 (4736): 405–7
Zarins CK, Zatina MA, Giddens DP, et al. Shear stress regulation of artery lumen diameter in experimentalatherogenesis. J Vasc Surg 1987; 5 (3): 413–20
Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med 1994; 330 (20): 1431–8
Tronc F, Wassef M, Esposito B, et al. Role of NO in flowinduced remodeling of the rabbit common carotid artery. Arterioscler Thromb Vasc Biol 1996; 16 (10): 1256–62
Rudic RD, Shesely EG, Maeda N, et al. Direct evidence for the importance of endothelium-derived nitric oxide invascular remodeling. J Clin Invest 1998; 101 (4): 731–6
Prior BM, Lloyd PG, Yang HT, et al. Exercise-induced vascular remodeling. Exerc Sport Sci Rev 2003; 31 (1): 26–33
Leon AS, Bloor CM. Effects of exercise and its cessation on the heart and its blood supply. J Appl Physiol 1968; 24 (4): 485–90
Kramsch DM, Aspen AJ, Abramowitz BM, et al. Reduction of coronary atherosclerosis by moderate conditioningexercise in monkeys on an atherogenic diet. N Engl J Med 1981; 305 (25): 1483–9
Miyachi M, Tanaka H, Yamamoto K, et al. Effects of onelegged endurance training on femoral arterial and venoussize in healthy humans. J Appl Physiol 2001; 90 (6): 2439–44
Holubkov R, Karas RH, Pepine CJ, et al. Large brachial artery diameter is associated with angiographic coronaryartery disease in women. Am Heart J 2002; 143 (5): 802–7
Glagov S, Zarins C, Giddens DP, et al. Hemodynamics and atherosclerosis: insights and perspectives gained fromstudies of human arteries. Arch Pathol Lab Med 1988; 112 (10): 1018–31
Labropoulos N, Zarge J, Mansour MA, et al. Compensatory arterial enlargement is a common pathobiologic responsein early atherosclerosis. Am J Surg 1998; 176 (2): 140–3
O’Rourke M. Mechanical principles in arterial disease. Hypertension 1995; 26 (1): 2–9
Owlya R, Vollenweider L, Trueb L, et al. Cardiovascular and sympathetic effects of nitric oxide inhibition at restand during static exercise in humans. Circulation 1997; 96 (11): 3897–903
Green DJ, Cable NT, Fox C, et al. Modification of forearm resistance vessels by exercise training in young men. J Appl Physiol 1994; 77 (4): 1829–33
Franke WD, Stephens GM, Schmid 3rd PG. Effects of intense exercise training on endothelium-dependent exercise-induced vasodilatation. Clin Physiol 1998; 18 (6): 521–8
Kingwell BA, Arnold PJ, Jennings GL, et al. Spontaneous running increases aortic compliance in Wistar-Kyoto rats. Cardiovasc Res 1997; 35 (1): 132–7
Maiorana A, O’Driscoll G, Dembo L, et al. Effect of aerobic and resistance exercise training on vascular functionin heart failure. Am J Physiol Heart Circ Physiol 2000; 279 (4): H1999–2005
Linke A, Schoene N, Gielen S, et al. Endothelial dysfunction in patients with chronic heart failure: systemic effectsof lower-limb exercise training. J Am Coll Cardiol 2001; 37 (2): 392–7
Walsh JH, Bilsborough W, Maiorana A, et al. Exercise training improves conduit vessel function in patients withcoronary artery disease. J Appl Physiol 2003; 95 (1): 20–5
Walsh JH, Yong G, Cheetham C, et al. Effects of exercise training on conduit and resistance vessel function intreated and untreated hypercholesterolaemic subjects. Eur Heart J 2003; 24 (18): 1681–9
Clapp BR, Hingorani AD, Kharbanda RK, et al. Inflammation-induced endothelial dysfunction involvesreduced nitric oxide bioavailability and increased oxidantstress. Cardiovasc Res 2004; 64 (1): 172–8
Stadtman ER. Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radic Biol Med 1990; 9 (4): 315–25
Soccio M, Toniato E, Evangelista V, et al. Oxidative stress and cardiovascular risk: the role of vascular NAD (P)Hoxidase and its genetic variants. Eur J Clin Invest 2005; 35 (5): 305–14
De Caterina R. Endothelial dysfunctions: common denominators in vascular disease. Curr Opin Lipidol 2000; 11 (1): 9–23
Higashi Y, Yoshizumi M. Exercise and endothelial function: role of endothelium-derived nitric oxide and oxidativestress in healthy subjects and hypertensive patients. Pharmacol Ther 2004; 102 (1): 87–96
Haram PM, Adams V, Kemi OJ, et al. Time-course of endothelial adaptation following acute and regular exercise. Eur J Cardiovasc Prev Rehabil 2006; 13 (4): 585–91
Chakraphan D, Sridulyakul P, Thipakorn B, et al. Attenuation of endothelial dysfunction by exercise trainingin STZ-induced diabetic rats. Clin Hemorheol Microcirc 2005; 32 (3): 217–26
Hollander J, Fiebig R, Gore M, et al. Superoxide dismutase gene expression is activated by a single bout of exercise inrat skeletal muscle. Pflugers Arch 2001; 442 (3): 426–34
Taddei S, Galetta F, Virdis A, et al. Physical activity prevents age-related impairment in nitric oxide availability inelderly athletes. Circulation 2000; 101 (25): 2896–901
Fukai T, Siegfried MR, Ushio-Fukai M, et al. Regulation of the vascular extracellular superoxide dismutase by nitricoxide and exercise training. J Clin Invest 2000; 105 (11): 1631–9
Walther C, Gielen S, Hambrecht R. The effect of exercise training on endothelial function in cardiovascular diseasein humans. Exerc Sport Sci Rev 2004; 32 (4): 129–34
Allen RG, Tresini M. Oxidative stress and gene regulation. Free Radic Biol Med 2000; 28 (3): 463–99
Franzoni F, Plantinga Y, Femia FR, et al. Plasma antioxidant activity and cutaneous microvascular endothelialfunction in athletes and sedentary controls. Biomed Pharmacother 2004; 58 (8): 432–6
Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev 1998; 78 (2): 547–81
Darley-Usmar V, Starke-Reed PE. Antioxidants: strategies for interventions in aging and age-related diseases. Aworkshop sponsored by the National Institute on Agingand by the Office of Dietary Supplements. Antioxid Redox Signal 2000; 2 (3): 375–7
Golden TR, Hinerfeld DA, Melov S. Oxidative stress and aging: beyond correlation. Aging Cell 2002; 1 (2): 117–23
Ji LL, Leeuwenburgh C, Leichtweis S, et al. Oxidative stress and aging: role of exercise and its influences on antioxidantsystems. Ann N Y Acad Sci 1998; 854: 102–17
Gomez-Cabrera MC, Domenech E, Vina J. Moderate exercise is an antioxidant: upregulation of antioxidant genesby training. Free Radic Biol Med 2008; 44 (2): 126–31
Salminen A, Vihko V. Endurance training reduces the susceptibility of mouse skeletal muscle to lipid peroxidationin vitro. Acta Physiol Scand 1983; 117 (1): 109–13
Petrone WF, English DK, Wong K, et al. Free radicals and inflammation: superoxide-dependent activation of aneutrophil chemotactic factor in plasma. Proc Natl Acad Sci USA 1980; 77 (2): 1159–63
Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979; 59 (3): 527–605
Alessio HM, Goldfarb AH, Cutler RG. MDA content increases in fast- and slow-twitch skeletal muscle with intensityof exercise in a rat. Am J Physiol 1988; 255 (6 Pt 1): C874–7
Ji LL, Fu R, Mitchell EW. Glutathione and antioxidant enzymes in skeletal muscle: effects of fiber type and exerciseintensity. J Appl Physiol 1992; 73 (5): 1854–9
Duarte JA, Appell HJ, Carvalho F, et al. Endotheliumderived oxidative stress may contribute to exerciseinducedmuscle damage. Int J Sports Med 1993; 14 (8): 440–3
Chevion S, Moran DS, Heled Y, et al. Plasma antioxidant status and cell injury after severe physical exercise. Proc Natl Acad Sci U S A 2003; 100 (9): 5119–23
Cicek D. Exercise and oxidative stress. Anadolu Kardiyol Derg 2006; 6 (2): 141–2
Lijnen HR, Collen D. Endothelium in hemostasis and thrombosis. Prog Cardiovasc Dis 1997; 39 (4): 343–50
Smith DT, Hoetzer GL, Greiner JJ, et al. Effects of ageing and regular aerobic exercise on endothelial fibrinolyticcapacity in humans. J Physiol 2003; 546 (Pt 1): 289–98
Shatos MA, Doherty JM, Stump DC, et al. Oxygen radicals generated during anoxia followed by reoxygenationreduce the synthesis of tissue-type plasminogen activatorand plasminogen activator inhibitor-1 in human endothelialcell culture. J Biol Chem 1990; 265 (33): 20443–8
Kugiyama K, Sakamoto T, Misumi I, et al. Transferable lipids in oxidized low-density lipoprotein stimulate plasminogenactivator inhibitor-1 and inhibit tissue-typeplasminogen activator release from endothelial cells. Circ Res 1993; 73 (2): 335–43
Diamond SL, Eskin SG, McIntire LV. Fluid flow stimulates tissue plasminogen activator secretion by culturedhuman endothelial cells. Science 1989; 243 (4897): 1483–5
Diamond SL, Sharefkin JB, Dieffenbach C, et al. Tissue plasminogen activator messenger RNA levels increase incultured human endothelial cells exposed to laminar shearstress. J Cell Physiol 1990; 143 (2): 364–71
Kooistra T, Schrauwen Y, Arts J, et al. Regulation of endothelial cell t-PA synthesis and release. Int J Hematol 1994; 59 (4): 233–55
Laughlin MH, Oltman CL, Bowles DK. Exercise traininginduced adaptations in the coronary circulation. Med Sci Sports Exerc 1998; 30 (3): 352–60
Otsuki T, Maeda S, Iemitsu M, et al. Effects of athletic strength and endurance exercise training in young humanson plasma endothelin-1 concentration and arterialdistensibility. Exp Biol Med (Maywood) 2006; 231 (6): 789–93
Maeda S, Tanabe T, Miyauchi T, et al. Aerobic exercise training reduces plasma endothelin-1 concentration inolder women. J Appl Physiol 2003; 95 (1): 336–41
Rubanyi GM, Polokoff MA. Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol Rev 1994; 46 (3): 325–415
Maeda S, Tanabe T, Otsuki T, et al. Moderate regular exercise increases basal production of nitric oxide in elderlywomen. Hypertens Res 2004; 27 (12): 947–53
Cameron JD, Dart AM. Exercise training increases total systemic arterial compliance in humans. Am J Physiol 1994; 266 (2 Pt 2): H693–701
Kakiyama T, Sugawara J, Murakami H, et al. Effects of short-term endurance training on aortic distensibility inyoung males. Med Sci Sports Exerc 2005; 37 (2): 267–71
Miyachi M, Kawano H, Sugawara J, et al. Unfavorable effects of resistance training on central arterial compliance:a randomized intervention study. Circulation 2004; 110 (18): 2858–63
Bertovic DA, Waddell TK, Gatzka CD, et al. Muscular strength training is associated with low arterial complianceand high pulse pressure. Hypertension 1999; 33 (6): 1385–91
Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol 1999; 61: 391–415
Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelialcells. Nature 1988; 332 (6163): 411–5
Miyauchi T, Tomobe Y, Shiba R, et al. Involvement of endothelin in the regulation of human vascular tonus:potent vasoconstrictor effect and existence in endothelialcells. Circulation 1990; 81 (6): 1874–80
Komuro I, Kurihara H, Sugiyama T, et al. Endothelin stimulates c-fos and c-myc expression and proliferation ofvascular smooth muscle cells. FEBS Lett 1988; 238 (2): 249–52
MacDougall JD, McKelvie RS, Moroz DE, et al. Factors affecting blood pressure during heavy weight lifting andstatic contractions. J Appl Physiol 1992; 73 (4): 1590–7
Maeda S, Miyauchi T, Kakiyama T, et al. Effects of exercise training of 8 weeks and detraining on plasma levelsof endothelium-derived factors, endothelin-1 and nitricoxide, in healthy young humans. Life Sci 2001; 69 (9): 1005–16
Lee JS, Feldman AM. Gene therapy for therapeutic myocardial angiogenesis: a promising synthesis of two emergingtechnologies. Nat Med 1998; 4 (6): 739–42
Richardson RS, Wagner H, Mudaliar SR, et al. Exercise adaptation attenuates VEGF gene expression in humanskeletal muscle. Am J Physiol Heart Circ Physiol 2000; 279 (2): H772–8
Park JE, Keller GA, Ferrara N. The vascular endothelial growth factor (VEGF) isoforms: differential depositioninto the subepithelial extracellular matrix and bioactivityof extracellular matrix-bound VEGF. Mol Biol Cell 1993; 4 (12): 1317–26
Poltorak Z, Cohen T, Neufeld G. The VEGF splice variants: properties, receptors, and usage for the treatment ofischemic diseases. Herz 2000; 25 (2): 126–9
Gustafsson T, Puntschart A, Kaijser L, et al. Exerciseinduced expression of angiogenesis-related transcriptionand growth factors in human skeletal muscle. Am J Physiol 1999; 276 (2 Pt 2): H679–85
Richardson RS, Wagner H, Mudaliar SR, et al. Human VEGF gene expression in skeletal muscle: effect ofacute normoxic and hypoxic exercise. Am J Physiol 1999; 277 (6 Pt 2): H2247–52
Leung DW, Cachianes G, Kuang WJ, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989; 246 (4935): 1306–9
Brodal P, Ingjer F, Hermansen L. Capillary supply of skeletal muscle fibers in untrained and endurance-trainedmen. Am J Physiol 1977; 232 (6): H705–12
Hang J, Kong L, Gu JW, et al. VEGF gene expression is upregulated in electrically stimulated rat skeletal muscle. Am J Physiol 1995; 269 (5 Pt 2): H1827–31
Zumstein A, Mathieu O, Howald H, et al. Morphometric analysis of the capillary supply in skeletal muscles oftrained and untrained subjects: its limitations in musclebiopsies. Pflugers Arch 1983; 397 (4): 277–83
Bebout DE, Hogan MC, Hempleman SC, et al. Effects of training and immobilization on V̇O2 and DO2 in doggastrocnemius muscle in situ. J Appl Physiol 1993; 74 (4): 1697–703
Breen EC, Johnson EC, Wagner H, et al. Angiogenic growth factor mRNA responses in muscle to a single boutof exercise. J Appl Physiol 1996; 81 (1): 355–61
Keck PJ, Hauser SD, Krivi G, et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989; 246 (4935): 1309–12
Dimmeler S, Aicher A, Vasa M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cellsvia the PI 3-kinase/Akt pathway. J Clin Invest 2001; 108 (3): 391–7
Strehlow K, Werner N, Berweiler J, et al. Estrogen increases bone marrow-derived endothelial progenitor cellproduction and diminishes neointima formation. Circulation 2003; 107 (24): 3059–65
Yen MH, Yang JH, Sheu JR, et al. Chronic exercise enhances endothelium-mediated dilation in spontaneouslyhypertensive rats. Life Sci 1995; 57 (24): 2205–13
Wilson JR, Kapoor SC. Contribution of prostaglandins to exercise-induced vasodilation in humans. Am J Physiol 1993; 265 (1 Pt 2): H171–5
Hamberg M, Svensson J, Samuelsson B. Thromboxanes: a new group of biologically active compounds derived fromprostaglandin endoperoxides. Proc Natl Acad Sci U S A 1975; 72 (8): 2994–8
Moncada S, Higgs EA, Vane JR. Human arterial and venous tissues generate prostacyclin (prostaglandin x), apotent inhibitor of platelet aggregation. Lancet 1977; 1 (8001): 18–20
Gryglewski RJ, Bunting S, Moncada S, et al. Arterial walls are protected against deposition of platelet thrombi by asubstance (prostaglandin X) which they make fromprostaglandin endoperoxides. Prostaglandins 1976; 12 (5): 685–713
Wennmalm A, Fitzgerald GA. Excretion of prostacyclin and thromboxane A2 metabolites during leg exercise inhumans. Am J Physiol 1988; 255 (1 Pt 2): H15–8
Vesterqvist O. Measurements of the in vivo synthesis of thromboxane and prostacyclin in humans. Scand J Clin Lab Invest 1988; 48 (5): 401–7
Vesterqvist O, Green K. Development of a GC-MS method for quantitation of 2,3-dinor-6-keto-PGF1 alpha anddetermination of the urinary excretion rates in healthyhumans under normal conditions and following drugs. Prostaglandins 1984; 28 (1): 139–54
Ritter JM, Barrow SE, Blair IA, et al. Release of prostacyclin in vivo and its role in man. Lancet 1983; 1 (8320): 317–9
Frangos JA, Eskin SG, McIntire LV, et al. Flow effects on prostacyclin production by cultured human endothelialcells. Science 1985; 227 (4693): 1477–9
Durstine JL, Haskell WL. Effects of exercise training on plasma lipids and lipoproteins. Exerc Sport Sci Rev 1994; 22: 477–521
Rauramaa R. Physical activity and prostanoids. Acta Med Scand Suppl 1986; 711: 137–42
Stergioulas AT, Filippou DK. Effects of physical conditioning on lipids and arachidonic acid metabolites inuntrained boys: a longitudinal study. Appl Physiol Nutr Metab 2006; 31 (4): 432–41
Ronni-Sivula H, Malm H, Ylikorkala O, et al. Marathon run stimulates more prostacyclin than thromboxane synthesisand differently in men and women. Prostaglandins 1993; 46 (1): 75–9
Nakao J, Change WC, Murota SI, et al. Testosterone inhibits prostacyclin production by rat aortic smoothmuscle cells in culture. Atherosclerosis 1981; 39 (2): 203–9
Dessypris A, Kuoppasalmi K, Adlercreutz H. Plasma cortisol, testosterone, androstenedione and luteinizing hormone(LH) in a non-competitive marathon run. J Steroid Biochem 1976; 7 (1): 33–7
Tanaka H, Cleroux J, de Champlain J, et al. Persistent effects of a marathon run on the pituitary-testicular axis. J Endocrinol Invest 1986; 9 (2): 97–101
Keizer H, Janssen GM, Menheere P, et al. Changes in basal plasma testosterone, cortisol, and dehydroepiandrosteronesulfate in previously untrained males and femalespreparing for a marathon. Int J Sports Med 1989; 10 Suppl. 3: S139–45
Mathur RS, Neff MR, Landgrebe SC, et al. Time-related changes in the plasma concentrations of prolactin, gonadotropins,sex hormone-binding globulin, and certainsteroid hormones in female runners after a long-distancerace. Fertil Steril 1986; 46 (6): 1067–70
Petridou A, Chatzinikolaou A, Fatouros I, et al. Resistance exercise does not affect the serum concentrations of celladhesion molecules. Br J Sports Med 2007; 41 (2): 76–9; discussion 79
Wannamethee SG, Lowe GD, Whincup PH, et al. Physical activity and hemostatic and inflammatory variables inelderly men. Circulation 2002; 105 (15): 1785–90
Church TS, Barlow CE, Earnest CP, et al. Associations between cardiorespiratory fitness and C-reactiveprotein in men. Arterioscler Thromb Vasc Biol 2002; 22 (11): 1869–76
Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein and inflammatory markers:a systematic review. J Am Coll Cardiol 2005; 45 (10): 1563–9
Tisi PV, Hulse M, Chulakadabba A, et al. Exercise training for intermittent claudication: does it adversely affect biochemicalmarkers of the exercise-induced inflammatoryresponse? Eur J Vasc Endovasc Surg 1997; 14 (5): 344–50
Paffenbarger Jr RS, Hyde RT, Wing AL, et al. Physical activity, all-cause mortality, and longevity of collegealumni. N Engl J Med 1986; 314 (10): 605–13
Radak Z, Chung HY, Naito H, et al. Age-associated increase in oxidative stress and nuclear factor kappaB activationare attenuated in rat liver by regular exercise. FASEB J 2004; 18 (6): 749–50
McFarlin BK, Flynn MG, Phillips MD, et al. Chronic resistance exercise training improves natural killer cell activityin older women. J Gerontol A Biol Sci Med Sci 2005; 60 (10): 1315–8
Stewart LK, Flynn MG, Campbell WW, et al. Influence of exercise training and age on CD14+ cell-surface expressionof toll-like receptor 2 and 4. Brain Behav Immun 2005; 19 (5): 389–97
Dohi Y, Thiel MA, Buhler FR, et al. Activation of endothelial L-arginine pathway in resistance arteries: effect ofage and hypertension. Hypertension 1990; 16 (2): 170–9
Hongo K, Nakagomi T, Kassell NF, et al. Effects of aging and hypertension on endothelium-dependent vascular relaxationin rat carotid artery. Stroke 1988; 19 (7): 892–7
Mayhan WG, Faraci FM, Baumbach GL, et al. Effects of aging on responses of cerebral arterioles. Am J Physiol 1990; 258 (4 Pt 2): H1138–43
Moritoki H, Hosoki E, Ishida Y. Age-related decrease in endothelium-dependent dilator response to histamine inrat mesenteric artery. Eur J Pharmacol 1986; 126 (1-2): 61–7
Soltis EE. Effect of age on blood pressure and membranedependent vascular responses in the rat. Circ Res 1987; 61 (6): 889–97
Castelli WP. Cardiovascular disease in women. Am J Obstet Gynecol 1988; 158 (6 Pt 2): 1553–160, 1566-7
Simoncini T, De Caterina R, Genazzani AR. Selective estrogen receptor modulators: different actions on vascularcell adhesion molecule-1 (VCAM-1) expression inhuman endothelial cells. J Clin Endocrinol Metab 1999; 84 (2): 815–8
Venkov CD, Rankin AB, Vaughan DE. Identification of authentic estrogen receptor in cultured endothelialcells: a potential mechanism for steroid hormone regulationof endothelial function. Circulation 1996; 94 (4): 727–33
Karas RH, Patterson BL, Mendelsohn ME. Human vascular smooth muscle cells contain functional estrogen receptor. Circulation 1994; 89 (5): 1943–50
Wild RA. Estrogen: effects on the cardiovascular tree. Obstet Gynecol 1996; 87 (2 Suppl.): 27S-35S
Acknowledgements
No sources of funding were used in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Di Francescomarino, S., Sciartilli, A., Di Valerio, V. et al. The Effect of Physical Exercise on Endothelial Function. Sports Med 39, 797–812 (2009). https://doi.org/10.2165/11317750-000000000-00000
Published:
Issue Date:
DOI: https://doi.org/10.2165/11317750-000000000-00000