To compare the acute effects of ascorbic acid on vasodilation of veins and arteries in vivo.
Twenty-six healthy non-smokers and 23 healthy moderate smokers were recruited in this study. The dorsal hand vein compliance technique and flow-mediated dilation were used. Dose-response curves to bradykinin and sodium nitroprusside were constructed to test the endothelium-dependent and -independent relaxation before and after acute infusion of ascorbic acid.
Smokers had an impaired venodilation with bradykinin compared with non-smokers (68.3%±13.2% vs 93.7%±20.1%, respectively; P<0.05). Ascorbic acid administration in the dorsal hand vein significantly increased the venodilation with bradykinin in smokers (68.3%± 13.2% vs 89.5%±6.3% before and after infusion, respectively; P<0.05) but not in non-smokers (93.7%±20.1% vs 86.4%±12.4% before and after infusion, respectively). Similarly, the arterial response in smokers had an impaired endothelium-dependent dilation compared with that in non-smokers (8.8%±2.7% vs 15.2%±2.3%, respectively; P<0.05) and ascorbic acid restored this response in smokers (8.8%±2.7% vs 18.7%±6.5% before and after infusion, respectively; P<0.05), but no difference was seen in non-smokers (15.2%±2.3% vs 14.0%±4.4% before and after infusion, respectively). The endothelium-independent dilation did not differ in both the groups studied. No important hemodynamic change was detected using the Portapress device.
Smokers had impaired endothelium-dependent vasodilation responsiveness in both arterial and venous systems. Ascorbic acid restores this responsiveness in smokers.
Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, Robinson J, et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 1993; 88 ( 5 Pt 1): 2149–55.
Benowitz NL . Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment. Prog Cardiovasc Dis 2003; 46: 91–111.
Tanus-Santos JE, Toledo JC, Cittadino M, Sabha M, Rocha JC, Moreno H Jr . Cardiovascular effects of transdermal nicotine in mildly hypertensive smokers. Am J Hypertens 2001; 14 ( 7 Pt 1): 610–4.
Samet JM . The 1990 report of the surgeon general: the health benefits of smoking cessation. Am Rev Respir Dis 1990; 142: 993–4.
Sabha M, Tanus-Santos JE, Toledo JC, Cittadino M, Rocha JC, Moreno H Jr . Transdermal nicotine mimics the smoking-induced endothelial dysfunction. Clin Pharmacol Ther 2000; 68: 167–74.
Neunteufl T, Heher S, Kostner K, Mitulovic G, Lehr S, Khoschsorur G, et al. Contribution of nicotine to acute endothelial dysfunction in long-term smokers. J Am Coll Cardiol 2002; 39: 251–6.
Kalra J, Chaudhary AK, Prasad K . Increased production of oxygen free radicals in cigarette smokers. Int J Exp Pathol 1991; 72: 1–7.
Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SM, Shyr Y, et al. Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage. N Engl J Med 1995; 332: 1198–203.
Reilly M, Delanty N, Lawson JA, Fitz Gerald GA . Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation 1996; 94: 19–25.
Node K, Kitakaze M, Yoshikawa H, Kosaka H, Hori M . Reversible reduction in plasma concentration of nitric oxide induced by cigarette smoking in young adults. Am J Cardiol 1997; 79: 1538–41.
Tsuchiya M, Asada A, Kasahara E, Sato EF, Shindo M, Inoue M . Smoking a single cigarette rapidly reduces combined concentrations of nitrate and nitrite and concentrations of antioxidants in plasma. Circulation 2002; 105: 1155–7.
Frei B, England L, Ames BN . Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 1989; 86: 6377–81.
Heitzer T, Just H, Munzel T . Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation 1996; 94: 6–9.
Luscher TF, Diederich D, Siebenmann R, Lehmann K, Stulz P, von Segesser L, et al. Difference between endothelium-dependent relaxation in arterial and in venous coronary bypass grafts. N Engl J Med 1988; 319: 462–7.
Liu ZG, Ge ZD, He GW . Difference in endothelium-derived hyper-polarizing factor-mediated hyperpolarization and nitric oxide release between human internal mammary artery and saphenous vein. Circulation 2000; 102 ( 19 Suppl 3): III296–301.
Wagner L, Hoey JG, Erdely A, Boegehold MA, Baylis C . The nitric oxide pathway is amplified in venular vs arteriolar cultured rat mesenteric endothelial cells. Microvasc Res 2001; 62: 401–9.
Boegehold MA . Heterogeneity of endothelial function within the circulation. Curr Opin Nephrol Hypertens 1998; 7: 71–8.
Aellig WH . A new technique for recording compliance of human hand veins. 1981. Br J Clin Pharmacol 2004; 58: S768–74.
Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. 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: 257–65.
Landmesser U, Merten R, Spiekermann S, Buttner K, Drexler H, Hornig B . Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation 2000; 101: 2264–70.
Mackay D . A generally useful modification of ALLFIT that facilitates the fitting of null equations to dose-response curves. Trends Pharmacol Sci 1988; 9: 121–2.
Vallance P, Collier J, Moncada S . Nitric oxide synthesised from L-arginine mediates endothelium dependent dilation in human veins in vivo. Cardiovasc Res 1989; 23: 1053–7.
Bedarida GV, Kim D, Blaschke TF, Hoffman BB . Characterization of an inhibitor of nitric oxide synthase in human-hand veins. Horm Metab Res 1994; 26: 109–12.
Bohlen HG . Mechanism of increased vessel wall nitric oxide concentrations during intestinal absorption. Am J Physiol 1998; 275 ( 2 Pt2): H542–50.
Fukaya Y, Ohhashi T . Acetylcholine- and flow-induced production and release of nitric oxide in arterial and venous endothelial cells. Am J Physiol 1996; 270 ( 1 Pt 2): H99–106.
Kuo L, Arko F, Chilian WM, Davis MJ . Coronary venular responses to flow and pressure. Circ Res 1993; 72: 607–15.
Mangoush O, Nakamura K, Al-Ruzzeh S, Athanasiou T, Chester A, Amrani M . Effect of ascorbic acid on endothelium-dependent vasodilation of human arterial conduits for coronary artery bypass grafting. Eur J Cardiothorac Surg 2003; 24: 541–6.
Komori K, Inoguchi H, Kume M, Shoji T, Furuyama T . Differences in endothelial function and morphologic modulation between canine autogenous venous and arterial grafts: endothelium and intimal thickening. Surgery 2002; 131 ( 1 Suppl): S249–55.
Yang ZH, von Segesser, L, Bauer E, Stulz P, Turina M, Luscher TF . Different activation of the endothelial L-arginine and cyclooxygenase pathway in the human internal mammary artery and saphenous vein. Circ Res 1991; 68: 52–60.
Moreno H Jr, Chalon S, Urae A, Tangphao O, Abiose AK, Hoffman BB, et al. Endothelial dysfunction in human hand veins is rapidly reversible after smoking cessation. Am J Physiol 1998; 275 ( 3 Pt 2): H1040–45.
Yugar-Toledo JC, Tanus-Santos JE, Sabha M, Sousa MG, Cittadino M, Tacito LH, et al. Uncontrolled hypertension, uncompensated type II diabetes, and smoking have different patterns of vascular dysfunction. Chest 2004; 125: 823–30.
Schectman G, Byrd JC, Gruchow HW . The influence of smoking on vitamin C status in adults. Am J Public Health 1989; 79: 158–62.
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: 2673–8.
Chambers JC, McGregor A, Jean-Marie J, Obeid OA, Kooner JS . Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation 1999; 99: 1156–60.
Perticone F, Ceravolo R, Maio R, Cloro C, Candigliota M, Scozzafava A, et al. Effects of atorvastatin and vitamin C on endothelial function of hypercholesterolemic patients. Atherosclerosis 2000; 152: 511–8.
Sherman DL, Keaney JF Jr, Biegelsen ES, Duffy SJ, Coffman JD, Vita JA . Pharmacological concentrations of ascorbic acid are required for the beneficial effect on endothelial vasomotor function in hypertension. Hypertension 2000; 35: 936–41.
Hirai N, Kawano H, Hirashima O, Motoyama T, Moriyama Y, Sakamoto T, et al. Insulin resistance and endothelial dysfunction in smokers: effects of vitamin C. Am J Physiol Heart Circ Physiol 2000; 279: H1172–8.
May JM . How does ascorbic acid prevent endothelial dysfunction? Free Radic Biol Med 2000; 28: 1421–9.
Project supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), São Paulo, Brazil.
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Gonçalves de Sousa, M., Yugar-Toledo, J., Rubira, M. et al. Ascorbic acid improves impaired venous and arterial endothelium-dependent dilation in smokers. Acta Pharmacol Sin 26, 447–452 (2005). https://doi.org/10.1111/j.1745-7254.2005.00069.x
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