The effect of oral antioxidants on brachial artery flow-mediated dilation following 5 and 10 min of ischemia

Ryan A. Harris; Steven K Nishiyama; D. Walter Wray; Vince Tedjasaputra; Damian M Bailey; Russell S Richardson

doi:10.1007/s00421-009-1147-x

The effect of oral antioxidants on brachial artery flow-mediated dilation following 5 and 10 min of ischemia

Ryan A. Harris, Steven K Nishiyama, D. Walter Wray, Vince Tedjasaputra, Damian M Bailey, Russell S Richardson

Research output: Contribution to journal › Article › peer-review

Abstract

In light of the current methodological developments in flow-mediated dilation (FMD) testing and the recognition that oxidative stress may play an important role in regulating this process, the present study sought to: (1) compare flow-mediated dilation (FMD) following 5 and 10 min of forearm cuff occlusion, and (2) evaluate the role of oxidative stress on vasodilation, both distal and proximal to the cuff. Of the 14 subjects studied, 6 partook solely in a validation study of the antioxidant cocktail (AOC; vitamins C, E, and alpha-lipoic acid), while the remaining 8 subjects underwent FMD assessment in response to 5 and 10 min of forearm occlusion following ingestion of AOC or placebo. Although the efficacy of the AOC was clearly documented by elevated plasma ascorbate levels (approximately 95%) and a reduced free radical concentration (approximately 65%), no effects of acute oral antioxidants were observed. FMD was significantly augmented in response to 10 min of forearm occlusion when compared to 5 min, whether expressed as % change (10.1 +/- 2 vs. 4.5 +/- 1%, respectively) or absolute change in diameter (0.035 +/- 0.005 vs. 0.018 +/- 0.005 cm, respectively). Additionally, post-occlusion shear rate (28,640 +/- 2,799 vs. 18,629 +/- 1,724/s, AUC), FMD/shear rate (approximately 50%), and time to peak dilation (68 +/- 7 vs. 53 +/- 8 s) were greater following 10 min of occlusion. In contrast to previous studies, this investigation has identified a greater brachial artery FMD in response to 10 versus 5 min of forearm ischemia, which appears to be unexplained by oxidative stress

Original language	English
Pages (from-to)	445-453
Journal	European Journal of Applied Physiology
Volume	107
DOIs	https://doi.org/10.1007/s00421-009-1147-x
Publication status	Published (in print/issue) - 11 Aug 2009

Bibliographical note

Reference text: Acree LS, Comp PC, Whitsett TL, Montgomery PS, Nickel KJ, Fjeldstad AS, Fjeldstad C, Gardner AW (2007) The influence of obesity on calf blood flow and vascular reactivity in older adults. Dyn Med 6:4
Agewall S, Hulthe J, Fagerberg B, Gottfridsson B, Wikstrand J (2002) Post-occlusion brachial artery vasodilatation after ischaemic handgrip exercise is nitric oxide mediated. Clin Physiol Funct
Imaging 22:18–23
Bailey DM, Davies B, Young IS, Jackson MJ, Davison GW, Isaacson R, Richardson RS (2003) EPR spectroscopic detection of free radical outflow from an isolated muscle bed in exercising
humans. J Appl Physiol 94:1714–1718
Bailey DM, Ainslie PN, Jackson SK, Richardson RS, Ghatei M (2004) Evidence against redox regulation of energy homoeostasis in humans at high altitude. Clin Sci (Lond) 107:589–600
Bellien J, Iacob M, Gutierrez L, Isabelle M, Lahary A, Thuillez C, Joannides R (2006) Crucial role of NO and endothelium-derived hyperpolarizing factor in human sustained conduit artery flowmediated
dilatation. Hypertension 48:1088–1094
Betik AC, Luckham VB, Hughson RL (2004) Flow-mediated dilation in human brachial artery after different circulatory occlusion conditions. Am J Physiol 286:H442–H448
Black MA, Cable NT, Thijssen DH, Green DJ (2008) Importance of measuring the time course of flow-mediated dilatation in humans. Hypertension 51:203–210
Corretti MC, Plotnick GD, Vogel RA (1995) Technical aspects of evaluating brachial artery vasodilatation using high-frequency ultrasound. Am J Physiol 268:H1397–H1404
Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F,
Creager MA, Deanfield J, Drexler H, Gehard-Herman M, Herrington D, Vallance P, Vita J, Vogel R (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated
vasodilation of the brachial artery. J Am Coll Cardiol 39:257–265
Darley-Usmar V, Wiseman H, Halliwell B (1995) Nitric oxide and oxygen radicals: a question of balance. FEBS Lett 369:131–135
Davies PF, Tripathi SC (1993) Mechanical stress mechanisms and the cell. An endothelial paradigm. Circ Res 72:239–245
Eskurza I, Monahan KD, Robinson JA, Seals DR (2004) Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol 556:315–324
Giraldez RR, Panda A, Xia Y, Sanders SP, Zweier JL (1997) Decreased nitric-oxide synthase activity causes impaired endothelium-dependent relaxation in the postischemic heart. J Biol Chem 272:21420–21426
Green D (2005) Point: flow-mediated dilation does reflect nitric oxide-mediated endothelial function. J Appl Physiol 99:1233–1234 (discussion 1237–1238)
Harris RA, Follett DH, Halliwell M, Wells PN (1991) Ultimate limits in ultrasonic imaging resolution. Ultrasound Med Biol 17:547–558
Harris RA, Padilla J, Rink LD, Wallace JP (2006) Variability of flowmediated dilation measurements with repetitive reactive hyperemia. Vasc Med 11:1–6
Imms FJ, Lee WS, Ludlow PG (1988) Reactive hyperaemia in the human forearm. Q J Exp Physiol 73:203–215
Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Luscher TF (1995) Nitric oxide is responsible for flowdependent dilatation of human peripheral conduit arteries in
vivo. Circulation 91:1314–1319
Johns RA, Linden JM, Peach MJ (1989) Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia. Circ Res
65:1508–1515
Kooijman M, Thijssen DHJ, de Groot PCE, Bleeker MWP, van
Kuppevelt HJM, Green DJ, Rongen GA, Smits P, Hopman MTE (2008) Flow-mediated dilatation in the superficial femoral artery is nitric oxide mediated in humans. J Physiol 586:1137–1145
Leeson P, Thorne S, Donald A, Mullen M, Clarkson P, Deanfield J (1997) Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli. Heart 78:22–27
Mitchell GF, Parise H, Vita JA, Larson MG, Warner E, Keaney JF Jr, Keyes MJ, Levy D, Vasan RS, Benjamin EJ (2004) Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study. Hypertension 44:134–139
Mullen MJ, Kharbanda RK, Cross J, Donald AE, Taylor M, Vallance P, Deanfield JE, MacAllister RJ (2001) Heterogenous nature of flow-mediated dilatation in human conduit arteries in vivo:
relevance to endothelial dysfunction in hypercholesterolemia. Circ Res 88:145–151
Neunteufl T, Kostner K, Katzenschlager R, Zehetgruber M, Maurer G, Weidinger F (1998) Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men. J Am Coll Cardiol 32:711–716
Nishiyama SK, Wray DW, Berkstresser K, Ramaswamy M, Richardson RS (2007) Limb-specific differences in flow-mediated dilation: the role of shear rate. J Appl Physiol 103:843–851
Plantinga Y, Ghiadoni L, Magagna A, Giannarelli C, Franzoni F, Taddei S, Salvetti A (2007) Supplementation with vitamins C and E improves arterial stiffness and endothelial function in
essential hypertensive patients. Am J Hypertens 20:392–397
Pleiner J, Schaller G, Mittermayer F, Marsik C, MacAllister RJ, Kapiotis S, Ziegler S, Ferlitsch A, Wolzt M (2008) Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemiareperfusion. Atherosclerosis 197:383–391
Pyke KE, Tschakovsky ME (2007) Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? J Appl Physiol 102:1510–1519
Pyke KE, Dwyer EM, Tschakovsky ME (2004) Impact of controlling shear rate on flow-mediated dilation responses in the brachial artery of humans. J Appl Physiol 97:499–508
Richardson RS, Donato AJ, Uberoi A, Wray DW, Lawrenson L, Nishiyama S, Bailey DM (2007) Exercise-induced brachial artery vasodilation: role of free radicals. Am J Physiol 292:H1516–H1522
Sinoway LI, Hendrickson C, Davidson WR Jr, Prophet S, Zelis R (1989) Characteristics of flow-mediated brachial artery vasodilation in human subjects. Circ Res 64:32–42
Szabo C (1996) The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock 6:79–88
Title LM, Cummings PM, Giddens K, Genest JJ Jr, Nassar BA (2000) Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll
Cardiol 36:758–765
Tschakovsky ME, Pyke KE (2005) Counterpoint: flow-mediated dilation does not reflect nitric oxide-mediated endothelial function. J Appl Physiol 99:1235–1237
Vuilleumier JP, Keck E (1993) Fluorometric assay of vitamin C in biological materials using a centrifugal analyser with fluorescence attachment. J Micronutr Anal 5:25–34
Wendelhag I, Fagerberg B, Wikstrand J (1999) Adding ischaemic hand exercise during occlusion of the brachial artery increases the flow-mediated vasodilation in ultrasound studies of endothelial
function. Clin Physiol 19:279–283
Woodman RJ, Playford DA, Watts GF, Cheetham C, Reed C, Taylor RR, Puddey IB, Beilin LJ, Burke V, Mori TA, Green D (2001) Improved analysis of brachial artery ultrasound using a novel
edge-detection software system. J Appl Physiol 91:929–937
Wray DW, Uberoi A, Lawrenson L, Richardson RS (2006) Evidence of preserved endothelial function and vascular plasticity with age. Am J Physiol 290:H1271–H1277
Wray DW, Uberoi A, Lawrenson L, Bailey DM, Richardson RS (2009) Oral antioxidants and cardiovascular health in the exercise-trained and untrained elderly: a radically different
outcome. Clin Sci 116:433–441 Zweier JL, Talukder MAH (2006) The role of oxidants and free
radicals in reperfusion injury. Cardiovasc Res 70:181–190

Keywords

Shear rate
Reactive hyperemia
Endothelial function
FMD
Antioxidants

Access to Document

10.1007/s00421-009-1147-x

http://uir.ulster.ac.uk/28342/1/art%253A10.1007%252Fs00421-009-1147-x.pdf

Cite this

@article{c44e55db1693445694f433b045fdc00d,

title = "The effect of oral antioxidants on brachial artery flow-mediated dilation following 5 and 10 min of ischemia",

abstract = "In light of the current methodological developments in flow-mediated dilation (FMD) testing and the recognition that oxidative stress may play an important role in regulating this process, the present study sought to: (1) compare flow-mediated dilation (FMD) following 5 and 10 min of forearm cuff occlusion, and (2) evaluate the role of oxidative stress on vasodilation, both distal and proximal to the cuff. Of the 14 subjects studied, 6 partook solely in a validation study of the antioxidant cocktail (AOC; vitamins C, E, and alpha-lipoic acid), while the remaining 8 subjects underwent FMD assessment in response to 5 and 10 min of forearm occlusion following ingestion of AOC or placebo. Although the efficacy of the AOC was clearly documented by elevated plasma ascorbate levels (approximately 95%) and a reduced free radical concentration (approximately 65%), no effects of acute oral antioxidants were observed. FMD was significantly augmented in response to 10 min of forearm occlusion when compared to 5 min, whether expressed as % change (10.1 +/- 2 vs. 4.5 +/- 1%, respectively) or absolute change in diameter (0.035 +/- 0.005 vs. 0.018 +/- 0.005 cm, respectively). Additionally, post-occlusion shear rate (28,640 +/- 2,799 vs. 18,629 +/- 1,724/s, AUC), FMD/shear rate (approximately 50%), and time to peak dilation (68 +/- 7 vs. 53 +/- 8 s) were greater following 10 min of occlusion. In contrast to previous studies, this investigation has identified a greater brachial artery FMD in response to 10 versus 5 min of forearm ischemia, which appears to be unexplained by oxidative stress",

keywords = "Shear rate, Reactive hyperemia, Endothelial function, FMD, Antioxidants",

author = "Harris, {Ryan A.} and Nishiyama, {Steven K} and Wray, {D. Walter} and Vince Tedjasaputra and Bailey, {Damian M} and Richardson, {Russell S}",

note = "Reference text: Acree LS, Comp PC, Whitsett TL, Montgomery PS, Nickel KJ, Fjeldstad AS, Fjeldstad C, Gardner AW (2007) The influence of obesity on calf blood flow and vascular reactivity in older adults. Dyn Med 6:4 Agewall S, Hulthe J, Fagerberg B, Gottfridsson B, Wikstrand J (2002) Post-occlusion brachial artery vasodilatation after ischaemic handgrip exercise is nitric oxide mediated. Clin Physiol Funct Imaging 22:18–23 Bailey DM, Davies B, Young IS, Jackson MJ, Davison GW, Isaacson R, Richardson RS (2003) EPR spectroscopic detection of free radical outflow from an isolated muscle bed in exercising humans. J Appl Physiol 94:1714–1718 Bailey DM, Ainslie PN, Jackson SK, Richardson RS, Ghatei M (2004) Evidence against redox regulation of energy homoeostasis in humans at high altitude. Clin Sci (Lond) 107:589–600 Bellien J, Iacob M, Gutierrez L, Isabelle M, Lahary A, Thuillez C, Joannides R (2006) Crucial role of NO and endothelium-derived hyperpolarizing factor in human sustained conduit artery flowmediated dilatation. Hypertension 48:1088–1094 Betik AC, Luckham VB, Hughson RL (2004) Flow-mediated dilation in human brachial artery after different circulatory occlusion conditions. Am J Physiol 286:H442–H448 Black MA, Cable NT, Thijssen DH, Green DJ (2008) Importance of measuring the time course of flow-mediated dilatation in humans. Hypertension 51:203–210 Corretti MC, Plotnick GD, Vogel RA (1995) Technical aspects of evaluating brachial artery vasodilatation using high-frequency ultrasound. Am J Physiol 268:H1397–H1404 Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gehard-Herman M, Herrington D, Vallance P, Vita J, Vogel R (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. J Am Coll Cardiol 39:257–265 Darley-Usmar V, Wiseman H, Halliwell B (1995) Nitric oxide and oxygen radicals: a question of balance. FEBS Lett 369:131–135 Davies PF, Tripathi SC (1993) Mechanical stress mechanisms and the cell. An endothelial paradigm. Circ Res 72:239–245 Eskurza I, Monahan KD, Robinson JA, Seals DR (2004) Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol 556:315–324 Giraldez RR, Panda A, Xia Y, Sanders SP, Zweier JL (1997) Decreased nitric-oxide synthase activity causes impaired endothelium-dependent relaxation in the postischemic heart. J Biol Chem 272:21420–21426 Green D (2005) Point: flow-mediated dilation does reflect nitric oxide-mediated endothelial function. J Appl Physiol 99:1233–1234 (discussion 1237–1238) Harris RA, Follett DH, Halliwell M, Wells PN (1991) Ultimate limits in ultrasonic imaging resolution. Ultrasound Med Biol 17:547–558 Harris RA, Padilla J, Rink LD, Wallace JP (2006) Variability of flowmediated dilation measurements with repetitive reactive hyperemia. Vasc Med 11:1–6 Imms FJ, Lee WS, Ludlow PG (1988) Reactive hyperaemia in the human forearm. Q J Exp Physiol 73:203–215 Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Luscher TF (1995) Nitric oxide is responsible for flowdependent dilatation of human peripheral conduit arteries in vivo. Circulation 91:1314–1319 Johns RA, Linden JM, Peach MJ (1989) Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia. Circ Res 65:1508–1515 Kooijman M, Thijssen DHJ, de Groot PCE, Bleeker MWP, van Kuppevelt HJM, Green DJ, Rongen GA, Smits P, Hopman MTE (2008) Flow-mediated dilatation in the superficial femoral artery is nitric oxide mediated in humans. J Physiol 586:1137–1145 Leeson P, Thorne S, Donald A, Mullen M, Clarkson P, Deanfield J (1997) Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli. Heart 78:22–27 Mitchell GF, Parise H, Vita JA, Larson MG, Warner E, Keaney JF Jr, Keyes MJ, Levy D, Vasan RS, Benjamin EJ (2004) Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study. Hypertension 44:134–139 Mullen MJ, Kharbanda RK, Cross J, Donald AE, Taylor M, Vallance P, Deanfield JE, MacAllister RJ (2001) Heterogenous nature of flow-mediated dilatation in human conduit arteries in vivo: relevance to endothelial dysfunction in hypercholesterolemia. Circ Res 88:145–151 Neunteufl T, Kostner K, Katzenschlager R, Zehetgruber M, Maurer G, Weidinger F (1998) Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men. J Am Coll Cardiol 32:711–716 Nishiyama SK, Wray DW, Berkstresser K, Ramaswamy M, Richardson RS (2007) Limb-specific differences in flow-mediated dilation: the role of shear rate. J Appl Physiol 103:843–851 Plantinga Y, Ghiadoni L, Magagna A, Giannarelli C, Franzoni F, Taddei S, Salvetti A (2007) Supplementation with vitamins C and E improves arterial stiffness and endothelial function in essential hypertensive patients. Am J Hypertens 20:392–397 Pleiner J, Schaller G, Mittermayer F, Marsik C, MacAllister RJ, Kapiotis S, Ziegler S, Ferlitsch A, Wolzt M (2008) Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemiareperfusion. Atherosclerosis 197:383–391 Pyke KE, Tschakovsky ME (2007) Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? J Appl Physiol 102:1510–1519 Pyke KE, Dwyer EM, Tschakovsky ME (2004) Impact of controlling shear rate on flow-mediated dilation responses in the brachial artery of humans. J Appl Physiol 97:499–508 Richardson RS, Donato AJ, Uberoi A, Wray DW, Lawrenson L, Nishiyama S, Bailey DM (2007) Exercise-induced brachial artery vasodilation: role of free radicals. Am J Physiol 292:H1516–H1522 Sinoway LI, Hendrickson C, Davidson WR Jr, Prophet S, Zelis R (1989) Characteristics of flow-mediated brachial artery vasodilation in human subjects. Circ Res 64:32–42 Szabo C (1996) The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock 6:79–88 Title LM, Cummings PM, Giddens K, Genest JJ Jr, Nassar BA (2000) Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 36:758–765 Tschakovsky ME, Pyke KE (2005) Counterpoint: flow-mediated dilation does not reflect nitric oxide-mediated endothelial function. J Appl Physiol 99:1235–1237 Vuilleumier JP, Keck E (1993) Fluorometric assay of vitamin C in biological materials using a centrifugal analyser with fluorescence attachment. J Micronutr Anal 5:25–34 Wendelhag I, Fagerberg B, Wikstrand J (1999) Adding ischaemic hand exercise during occlusion of the brachial artery increases the flow-mediated vasodilation in ultrasound studies of endothelial function. Clin Physiol 19:279–283 Woodman RJ, Playford DA, Watts GF, Cheetham C, Reed C, Taylor RR, Puddey IB, Beilin LJ, Burke V, Mori TA, Green D (2001) Improved analysis of brachial artery ultrasound using a novel edge-detection software system. J Appl Physiol 91:929–937 Wray DW, Uberoi A, Lawrenson L, Richardson RS (2006) Evidence of preserved endothelial function and vascular plasticity with age. Am J Physiol 290:H1271–H1277 Wray DW, Uberoi A, Lawrenson L, Bailey DM, Richardson RS (2009) Oral antioxidants and cardiovascular health in the exercise-trained and untrained elderly: a radically different outcome. Clin Sci 116:433–441 Zweier JL, Talukder MAH (2006) The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res 70:181–190",

year = "2009",

month = aug,

day = "11",

doi = "10.1007/s00421-009-1147-x",

language = "English",

volume = "107",

pages = "445--453",

journal = "European Journal of Applied Physiology",

issn = "1439-6327",

publisher = "Springer",

}

TY - JOUR

T1 - The effect of oral antioxidants on brachial artery flow-mediated dilation following 5 and 10 min of ischemia

AU - Harris, Ryan A.

AU - Nishiyama, Steven K

AU - Wray, D. Walter

AU - Tedjasaputra, Vince

AU - Bailey, Damian M

AU - Richardson, Russell S

N1 - Reference text: Acree LS, Comp PC, Whitsett TL, Montgomery PS, Nickel KJ, Fjeldstad AS, Fjeldstad C, Gardner AW (2007) The influence of obesity on calf blood flow and vascular reactivity in older adults. Dyn Med 6:4 Agewall S, Hulthe J, Fagerberg B, Gottfridsson B, Wikstrand J (2002) Post-occlusion brachial artery vasodilatation after ischaemic handgrip exercise is nitric oxide mediated. Clin Physiol Funct Imaging 22:18–23 Bailey DM, Davies B, Young IS, Jackson MJ, Davison GW, Isaacson R, Richardson RS (2003) EPR spectroscopic detection of free radical outflow from an isolated muscle bed in exercising humans. J Appl Physiol 94:1714–1718 Bailey DM, Ainslie PN, Jackson SK, Richardson RS, Ghatei M (2004) Evidence against redox regulation of energy homoeostasis in humans at high altitude. Clin Sci (Lond) 107:589–600 Bellien J, Iacob M, Gutierrez L, Isabelle M, Lahary A, Thuillez C, Joannides R (2006) Crucial role of NO and endothelium-derived hyperpolarizing factor in human sustained conduit artery flowmediated dilatation. Hypertension 48:1088–1094 Betik AC, Luckham VB, Hughson RL (2004) Flow-mediated dilation in human brachial artery after different circulatory occlusion conditions. Am J Physiol 286:H442–H448 Black MA, Cable NT, Thijssen DH, Green DJ (2008) Importance of measuring the time course of flow-mediated dilatation in humans. Hypertension 51:203–210 Corretti MC, Plotnick GD, Vogel RA (1995) Technical aspects of evaluating brachial artery vasodilatation using high-frequency ultrasound. Am J Physiol 268:H1397–H1404 Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gehard-Herman M, Herrington D, Vallance P, Vita J, Vogel R (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. J Am Coll Cardiol 39:257–265 Darley-Usmar V, Wiseman H, Halliwell B (1995) Nitric oxide and oxygen radicals: a question of balance. FEBS Lett 369:131–135 Davies PF, Tripathi SC (1993) Mechanical stress mechanisms and the cell. An endothelial paradigm. Circ Res 72:239–245 Eskurza I, Monahan KD, Robinson JA, Seals DR (2004) Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol 556:315–324 Giraldez RR, Panda A, Xia Y, Sanders SP, Zweier JL (1997) Decreased nitric-oxide synthase activity causes impaired endothelium-dependent relaxation in the postischemic heart. J Biol Chem 272:21420–21426 Green D (2005) Point: flow-mediated dilation does reflect nitric oxide-mediated endothelial function. J Appl Physiol 99:1233–1234 (discussion 1237–1238) Harris RA, Follett DH, Halliwell M, Wells PN (1991) Ultimate limits in ultrasonic imaging resolution. Ultrasound Med Biol 17:547–558 Harris RA, Padilla J, Rink LD, Wallace JP (2006) Variability of flowmediated dilation measurements with repetitive reactive hyperemia. Vasc Med 11:1–6 Imms FJ, Lee WS, Ludlow PG (1988) Reactive hyperaemia in the human forearm. Q J Exp Physiol 73:203–215 Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Luscher TF (1995) Nitric oxide is responsible for flowdependent dilatation of human peripheral conduit arteries in vivo. Circulation 91:1314–1319 Johns RA, Linden JM, Peach MJ (1989) Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia. Circ Res 65:1508–1515 Kooijman M, Thijssen DHJ, de Groot PCE, Bleeker MWP, van Kuppevelt HJM, Green DJ, Rongen GA, Smits P, Hopman MTE (2008) Flow-mediated dilatation in the superficial femoral artery is nitric oxide mediated in humans. J Physiol 586:1137–1145 Leeson P, Thorne S, Donald A, Mullen M, Clarkson P, Deanfield J (1997) Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli. Heart 78:22–27 Mitchell GF, Parise H, Vita JA, Larson MG, Warner E, Keaney JF Jr, Keyes MJ, Levy D, Vasan RS, Benjamin EJ (2004) Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study. Hypertension 44:134–139 Mullen MJ, Kharbanda RK, Cross J, Donald AE, Taylor M, Vallance P, Deanfield JE, MacAllister RJ (2001) Heterogenous nature of flow-mediated dilatation in human conduit arteries in vivo: relevance to endothelial dysfunction in hypercholesterolemia. Circ Res 88:145–151 Neunteufl T, Kostner K, Katzenschlager R, Zehetgruber M, Maurer G, Weidinger F (1998) Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men. J Am Coll Cardiol 32:711–716 Nishiyama SK, Wray DW, Berkstresser K, Ramaswamy M, Richardson RS (2007) Limb-specific differences in flow-mediated dilation: the role of shear rate. J Appl Physiol 103:843–851 Plantinga Y, Ghiadoni L, Magagna A, Giannarelli C, Franzoni F, Taddei S, Salvetti A (2007) Supplementation with vitamins C and E improves arterial stiffness and endothelial function in essential hypertensive patients. Am J Hypertens 20:392–397 Pleiner J, Schaller G, Mittermayer F, Marsik C, MacAllister RJ, Kapiotis S, Ziegler S, Ferlitsch A, Wolzt M (2008) Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemiareperfusion. Atherosclerosis 197:383–391 Pyke KE, Tschakovsky ME (2007) Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? J Appl Physiol 102:1510–1519 Pyke KE, Dwyer EM, Tschakovsky ME (2004) Impact of controlling shear rate on flow-mediated dilation responses in the brachial artery of humans. J Appl Physiol 97:499–508 Richardson RS, Donato AJ, Uberoi A, Wray DW, Lawrenson L, Nishiyama S, Bailey DM (2007) Exercise-induced brachial artery vasodilation: role of free radicals. Am J Physiol 292:H1516–H1522 Sinoway LI, Hendrickson C, Davidson WR Jr, Prophet S, Zelis R (1989) Characteristics of flow-mediated brachial artery vasodilation in human subjects. Circ Res 64:32–42 Szabo C (1996) The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock 6:79–88 Title LM, Cummings PM, Giddens K, Genest JJ Jr, Nassar BA (2000) Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 36:758–765 Tschakovsky ME, Pyke KE (2005) Counterpoint: flow-mediated dilation does not reflect nitric oxide-mediated endothelial function. J Appl Physiol 99:1235–1237 Vuilleumier JP, Keck E (1993) Fluorometric assay of vitamin C in biological materials using a centrifugal analyser with fluorescence attachment. J Micronutr Anal 5:25–34 Wendelhag I, Fagerberg B, Wikstrand J (1999) Adding ischaemic hand exercise during occlusion of the brachial artery increases the flow-mediated vasodilation in ultrasound studies of endothelial function. Clin Physiol 19:279–283 Woodman RJ, Playford DA, Watts GF, Cheetham C, Reed C, Taylor RR, Puddey IB, Beilin LJ, Burke V, Mori TA, Green D (2001) Improved analysis of brachial artery ultrasound using a novel edge-detection software system. J Appl Physiol 91:929–937 Wray DW, Uberoi A, Lawrenson L, Richardson RS (2006) Evidence of preserved endothelial function and vascular plasticity with age. Am J Physiol 290:H1271–H1277 Wray DW, Uberoi A, Lawrenson L, Bailey DM, Richardson RS (2009) Oral antioxidants and cardiovascular health in the exercise-trained and untrained elderly: a radically different outcome. Clin Sci 116:433–441 Zweier JL, Talukder MAH (2006) The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res 70:181–190

PY - 2009/8/11

Y1 - 2009/8/11

N2 - In light of the current methodological developments in flow-mediated dilation (FMD) testing and the recognition that oxidative stress may play an important role in regulating this process, the present study sought to: (1) compare flow-mediated dilation (FMD) following 5 and 10 min of forearm cuff occlusion, and (2) evaluate the role of oxidative stress on vasodilation, both distal and proximal to the cuff. Of the 14 subjects studied, 6 partook solely in a validation study of the antioxidant cocktail (AOC; vitamins C, E, and alpha-lipoic acid), while the remaining 8 subjects underwent FMD assessment in response to 5 and 10 min of forearm occlusion following ingestion of AOC or placebo. Although the efficacy of the AOC was clearly documented by elevated plasma ascorbate levels (approximately 95%) and a reduced free radical concentration (approximately 65%), no effects of acute oral antioxidants were observed. FMD was significantly augmented in response to 10 min of forearm occlusion when compared to 5 min, whether expressed as % change (10.1 +/- 2 vs. 4.5 +/- 1%, respectively) or absolute change in diameter (0.035 +/- 0.005 vs. 0.018 +/- 0.005 cm, respectively). Additionally, post-occlusion shear rate (28,640 +/- 2,799 vs. 18,629 +/- 1,724/s, AUC), FMD/shear rate (approximately 50%), and time to peak dilation (68 +/- 7 vs. 53 +/- 8 s) were greater following 10 min of occlusion. In contrast to previous studies, this investigation has identified a greater brachial artery FMD in response to 10 versus 5 min of forearm ischemia, which appears to be unexplained by oxidative stress

AB - In light of the current methodological developments in flow-mediated dilation (FMD) testing and the recognition that oxidative stress may play an important role in regulating this process, the present study sought to: (1) compare flow-mediated dilation (FMD) following 5 and 10 min of forearm cuff occlusion, and (2) evaluate the role of oxidative stress on vasodilation, both distal and proximal to the cuff. Of the 14 subjects studied, 6 partook solely in a validation study of the antioxidant cocktail (AOC; vitamins C, E, and alpha-lipoic acid), while the remaining 8 subjects underwent FMD assessment in response to 5 and 10 min of forearm occlusion following ingestion of AOC or placebo. Although the efficacy of the AOC was clearly documented by elevated plasma ascorbate levels (approximately 95%) and a reduced free radical concentration (approximately 65%), no effects of acute oral antioxidants were observed. FMD was significantly augmented in response to 10 min of forearm occlusion when compared to 5 min, whether expressed as % change (10.1 +/- 2 vs. 4.5 +/- 1%, respectively) or absolute change in diameter (0.035 +/- 0.005 vs. 0.018 +/- 0.005 cm, respectively). Additionally, post-occlusion shear rate (28,640 +/- 2,799 vs. 18,629 +/- 1,724/s, AUC), FMD/shear rate (approximately 50%), and time to peak dilation (68 +/- 7 vs. 53 +/- 8 s) were greater following 10 min of occlusion. In contrast to previous studies, this investigation has identified a greater brachial artery FMD in response to 10 versus 5 min of forearm ischemia, which appears to be unexplained by oxidative stress

KW - Shear rate

KW - Reactive hyperemia

KW - Endothelial function

KW - FMD

KW - Antioxidants

U2 - 10.1007/s00421-009-1147-x

DO - 10.1007/s00421-009-1147-x

M3 - Article

SN - 1439-6327

VL - 107

SP - 445

EP - 453

JO - European Journal of Applied Physiology

JF - European Journal of Applied Physiology

ER -

The effect of oral antioxidants on brachial artery flow-mediated dilation following 5 and 10 min of ischemia

Abstract

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