Abstract
Aging is associated with a pro-oxidant state and a decline in endothelial function. Whether acute, enteral antioxidant treatment can reverse this decrement in vascular function is not well known. Flow-mediated vasodilation and reactive hyperemia were evaluated after consumption of either placebo or an oral antioxidant cocktail (vitamin C, 1000mg; vitamin E, 600 IU; -lipoic acid, 600 mg) in 87 healthy volunteers (42 young: 251 years; 45 older: 711 years) using a double-blind, crossover design. Blood velocity and brachial artery diameter (ultrasound Doppler) were assessed before and after 5-minute forearm circulatory arrest. Serum markers of lipid peroxidation, total antioxidant capacity, endogenous antioxidant activity, and vitamin C were assayed, and plasma nitrate, nitrite, and 3-nitrotyrosine were determined. In the placebo trial, an age-related reduction in brachial artery vasodilation was evident (young: 7.40.6%; older: 5.20.4%). After antioxidant consumption, flow-mediated vasodilation improved in older subjects (placebo: 5.20.4%; antioxidant: 8.20.6%) but declined in the young (placebo: 7.40.6%; antioxidant: 5.80.6%). Reactive hyperemia was reduced with age, but antioxidant administration did not alter the response in either group. Together,these data demonstrate that antioxidant consumption acutely restores endothelial function in the elderly while disrupting normal endothelium-dependent vasodilation in the young and suggest that this age-related impairment is attributed, at least in part, to free radicals.
| Original language | English |
|---|---|
| Pages (from-to) | 818-824 |
| Journal | Hypertension |
| Volume | 59 |
| DOIs | |
| Publication status | Published (in print/issue) - 21 Feb 2012 |
Bibliographical note
Reference text: 1. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993;90:7915–7922.
2. Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science. 1996;273:59–63.
3. Vanhoutte PM. Ageing and endothelial dysfunction. Eur Heart J. 2002; 49(suppl)A8–A17.
4. Taddei S, Galetta F, Virdis A, Ghiadoni L, Salvetti G, Franzoni F, Giusti C, Salvetti A. Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation. 2000;101:2896–2901.
5. Spier SA, Delp MD, Meininger CJ, Donato AJ, Ramsey MW, Muller-Delp JM. Effects of ageing and exercise training on endotheliumdependentvasodilatation and structure of rat skeletal muscle arterioles. J Physiol. 2004;556:947–958.
6. Chauhan A, More RS, Mullins PA, Taylor G, Petch C, Schofield PM. Aging-associated endothelial dysfunction in humans is reversed by l-arginine. J Am Coll Cardiol. 1996;28:1796–1804.
7. van der Loo B, Labugger R, Skepper JN, Bachschmid M, Kilo J, Powell JM, Palacios-Callender M, Erusalimsky JD, Quaschning T, Malinski T, Gygi D, Ullrich V, Luscher TF. Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med. 2000;192:1731–1744.
8. Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation. 2001;104:2673–2678.
9. Kris-Etherton PM, Lichtenstein AH, Howard BV, Steinberg D, Witztum JL. Antioxidant vitamin supplements and cardiovascular disease. Circulation. 2004;110:637–641.
10. Eskurza I, Monahan KD, Robinson JA, Seals DR. Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol. 2004;556:315–324.
11. Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A, Salvetti A. Age-related reduction of no availability and oxidative stress in humans. Hypertension. 2001;38:274–279.
12. Jablonski KL, Seals DR, Eskurza I, Monahan KD, Donato AJ. High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men. J Appl Physiol. 2007;103: 1715–1721.
13. Crecelius AR, Kirby BS, Voyles WF, Dinenno FA. Nitric oxide but not vasodilating prostaglandins contributes to the improvement of exercise hyperemia via ascorbic acid in healthy older adults. Am J Physiol Heart Circ Physiol. 2010;299:H1633–H441.
14. Kirby BS, Voyles WF, Simpson CB, Carlson RE, Schrage WG, Dinenno FA. Endothelium-dependent vasodilatation and exercise hyperaemia in ageing humans: Impact of acute ascorbic acid administration. J Physiol. 2009;587:1989–2003.
15. Eskurza I, Myerburgh LA, Kahn ZD, Seals DR. Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults. J Physiol. 2005;568:1057–1065.
16. Doshi SN, Naka KK, Payne N, Jones CJ, Ashton M, Lewis MJ, Goodfellow J. Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide. Clin Sci. 2001;101: 629–635.
17. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC, Selwyn AP. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26:1235–1241.
18. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000;101:1899–1906.
19. Yeboah J, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, Lima JA, Crouse JR, Herrington DM. 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: 502–509.
20. Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO, Vita JA. Predictive value of noninvasively determined
endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. 2003;41:1769–1775.
21. Huang A, Sun D, Kaley G, Koller A. Superoxide released to high intra-arteriolar pressure reduces nitric oxide–mediated shear stress– and agonist-induced dilations. Circ Res. 1998;83:960–965.
22. Tagawa T, Imaizumi T, Endo T, Shiramoto M, Harasawa Y, Takeshita A. Role of nitric oxide in reactive hyperemia in human forearm vessels. Circulation. 1994;90:2285–2290.
23. Meredith IT, Currie KE, Anderson TJ, Roddy MA, Ganz P, Creager MA. Postischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide. Am J Physiol. 1996;270: H1435–H1440.
24. Harris RA, Nishiyama SK, Wray DW, Richardson RS. Ultrasound assessment of flow-mediated dilation. Hypertension. 2010;55: 1075–1085.
25. Richardson RS, Donato AJ, Uberoi A, Wray DW, Lawrenson L, Nishiyama S, Bailey DM. Exercise-induced brachial artery vasodilation: role of free radicals. Am J Physiol Heart Circ Physiol. 2007;292: H1516–H1522.
26. Wray DW, Uberoi A, Lawrenson L, Bailey DM, Richardson RS. Oral antioxidants and cardiovascular health in the exercise-trained anduntrained elderly: a radically different outcome. Clin Sci (Lond). 2009; 116:433–441.
27. Harris RA, Nishiyama SK, Wray DW, Tedjasaputra V, Bailey DM, Richardson RS. The effect of oral antioxidants on brachial artery flowmediated dilation following 5 and 10 min of ischemia. Eur J Appl Physiol. 2009;107:445–453.
28. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111–1115.
29. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39:257–265.
30. Vita JA, Keaney JF Jr. Endothelial function: a barometer for cardiovascular risk? Circulation. 2002;106:640–642.
31. Gerhard M, Roddy MA, Creager SJ, Creager MA. Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans. Hypertension. 1996;27:849–853.
32. Benjamin EJ, Larson MG, Keyes MJ, Mitchell GF, Vasan RS, Keaney JF Jr, Lehman BT, Fan S, Osypiuk E, Vita JA. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation. 2004;109:613–619.
33. Celermajer DS, Sorensen KE, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Deanfield JE. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol. 1994;24:471–476.
34. Wray DW, Nishiyama SK, Donato AJ, Carlier P, Bailey DM, Uberoi A, Richardson RS. The paradox of oxidative stress and exercise with advancing age. Exerc Sport Sci Rev. 2011;39:68–76. 35. Donato AJ, Uberoi A, Bailey DM, Wray DW, Richardson RS. Exerciseinduced brachial artery vasodilation: effects of antioxidants and exercise training in elderly men. Am J Physiol Heart Circ Physiol. 2010;298: H671–H678.
36. Lucchesi PA, Belmadani S, Matrougui K. Hydrogen peroxide acts as both vasodilator and vasoconstrictor in the control of perfused mouse mesenteric resistance arteries. J Hypertens. 2005;23:571–579.
37. Liu Y, Zhao H, Li H, Kalyanaraman B, Nicolosi AC, Gutterman DD. Mitochondrial sources of H2O2 generation play a key role in flowmediated
dilation in human coronary resistance arteries. Circulation Research. 2003;93:573–580.
38. Ristow M, Zarse K, Oberbach A, Kloting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Bluher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009;106:8665–8670.
39. Rubinshtein R, Kuvin JT, Soffler M, Lennon RJ, Lavi S, Nelson RE, Pumper GM, Lerman LO, Lerman A. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J. 2010;31:1142–1148.
40. Markel TA, Daley JC, Daley JC III, Hogeman CS, Herr MD, Khan MH, Gray KS, Kunselman AR, Sinoway LI. Aging and the exercise pressor reflex in humans. Circulation. 2003;107:675–678.
41. Leeuwenburgh C, Hansen P, Shaish A, Holloszy JO, Heinecke JW. Markers of protein oxidation by hydroxyl radical and reactive nitrogen species in tissues of aging rats. Am J Physiol. 1998;274:R453–R461.
42. Kleinbongard P, Dejam A, Lauer T, Rassaf T, Schindler A, Picker O, Scheeren T, Godecke A, Schrader J, Schulz R, Heusch G, Schaub GA, Bryan NS, Feelisch M, Kelm M. Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. Free Radic Biol Med. 2003;35:
790–796.
43. Halliwell B, Zhao K, Whiteman M. Nitric oxide and peroxynitrite. The ugly, the uglier and the not so good: a personal view of recent controversies. Free Radic Res. 1999;31:651–669.
Keywords
- aging
- endothelium
- free radicals
- NO
- vascular
