Original Article | Published:

Cardiovascular Pharmacology

Ascorbic acid improves impaired venous and arterial endothelium-dependent dilation in smokers

Acta Pharmacologica Sinica volume 26, pages 447452 (2005) | Download Citation

Project supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), São Paulo, Brazil.

Subjects

Abstract

Aim:

To compare the acute effects of ascorbic acid on vasodilation of veins and arteries in vivo.

Methods:

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.

Results:

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.

Conclusion:

Smokers had impaired endothelium-dependent vasodilation responsiveness in both arterial and venous systems. Ascorbic acid restores this responsiveness in smokers.

References

  1. 1.

    , , , , , 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.

  2. 2.

    . Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment. Prog Cardiovasc Dis 2003; 46: 91–111.

  3. 3.

    , , , , , . Cardiovascular effects of transdermal nicotine in mildly hypertensive smokers. Am J Hypertens 2001; 14 ( 7 Pt 1): 610–4.

  4. 4.

    . The 1990 report of the surgeon general: the health benefits of smoking cessation. Am Rev Respir Dis 1990; 142: 993–4.

  5. 5.

    , , , , , . Transdermal nicotine mimics the smoking-induced endothelial dysfunction. Clin Pharmacol Ther 2000; 68: 167–74.

  6. 6.

    , , , , , et al. Contribution of nicotine to acute endothelial dysfunction in long-term smokers. J Am Coll Cardiol 2002; 39: 251–6.

  7. 7.

    , , . Increased production of oxygen free radicals in cigarette smokers. Int J Exp Pathol 1991; 72: 1–7.

  8. 8.

    , , , , , 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.

  9. 9.

    , , , . Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation 1996; 94: 19–25.

  10. 10.

    , , , , . Reversible reduction in plasma concentration of nitric oxide induced by cigarette smoking in young adults. Am J Cardiol 1997; 79: 1538–41.

  11. 11.

    , , , , , . Smoking a single cigarette rapidly reduces combined concentrations of nitrate and nitrite and concentrations of antioxidants in plasma. Circulation 2002; 105: 1155–7.

  12. 12.

    , , . Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 1989; 86: 6377–81.

  13. 13.

    , , . Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation 1996; 94: 6–9.

  14. 14.

    , , , , , et al. Difference between endothelium-dependent relaxation in arterial and in venous coronary bypass grafts. N Engl J Med 1988; 319: 462–7.

  15. 15.

    , , . 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.

  16. 16.

    , , , , . The nitric oxide pathway is amplified in venular vs arteriolar cultured rat mesenteric endothelial cells. Microvasc Res 2001; 62: 401–9.

  17. 17.

    . Heterogeneity of endothelial function within the circulation. Curr Opin Nephrol Hypertens 1998; 7: 71–8.

  18. 18.

    . A new technique for recording compliance of human hand veins. 1981. Br J Clin Pharmacol 2004; 58: S768–74.

  19. 19.

    , , , , , 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.

  20. 20.

    , , , , , . Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation 2000; 101: 2264–70.

  21. 21.

    . A generally useful modification of ALLFIT that facilitates the fitting of null equations to dose-response curves. Trends Pharmacol Sci 1988; 9: 121–2.

  22. 22.

    , , . Nitric oxide synthesised from L-arginine mediates endothelium dependent dilation in human veins in vivo. Cardiovasc Res 1989; 23: 1053–7.

  23. 23.

    , , , . Characterization of an inhibitor of nitric oxide synthase in human-hand veins. Horm Metab Res 1994; 26: 109–12.

  24. 24.

    . Mechanism of increased vessel wall nitric oxide concentrations during intestinal absorption. Am J Physiol 1998; 275 ( 2 Pt2): H542–50.

  25. 25.

    , . 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.

  26. 26.

    , , , . Coronary venular responses to flow and pressure. Circ Res 1993; 72: 607–15.

  27. 27.

    , , , , , . 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.

  28. 28.

    , , , , . 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.

  29. 29.

    , , , , , . 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.

  30. 30.

    , , , , , et al. Endothelial dysfunction in human hand veins is rapidly reversible after smoking cessation. Am J Physiol 1998; 275 ( 3 Pt 2): H1040–45.

  31. 31.

    , , , , , et al. Uncontrolled hypertension, uncompensated type II diabetes, and smoking have different patterns of vascular dysfunction. Chest 2004; 125: 823–30.

  32. 32.

    , , . The influence of smoking on vitamin C status in adults. Am J Public Health 1989; 79: 158–62.

  33. 33.

    , , , , . Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001; 104: 2673–8.

  34. 34.

    , , , , . Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation 1999; 99: 1156–60.

  35. 35.

    , , , , , et al. Effects of atorvastatin and vitamin C on endothelial function of hypercholesterolemic patients. Atherosclerosis 2000; 152: 511–8.

  36. 36.

    , , , , , . Pharmacological concentrations of ascorbic acid are required for the beneficial effect on endothelial vasomotor function in hypertension. Hypertension 2000; 35: 936–41.

  37. 37.

    , , , , , et al. Insulin resistance and endothelial dysfunction in smokers: effects of vitamin C. Am J Physiol Heart Circ Physiol 2000; 279: H1172–8.

  38. 38.

    . How does ascorbic acid prevent endothelial dysfunction? Free Radic Biol Med 2000; 28: 1421–9.

Download references

Author information

Affiliations

  1. Cardiovascular Pharmacology and Cardiology, Clinical Hospital of Campinas and Faculty of Medical Sciences, State University of Campinas, 13081-970, Campinas, São Paulo, Brazil

    • Márcio Gonçalves de Sousa
    • , Juan Carlos Yugar-Toledo
    • , Sílvia Elaine Ferreira-Melo
    • , Deise Barbieri
    •  & Heitor Moreno Jr
  2. Hypertension Unit, InCor, Clinical Hospital of São Paulo, Faculty of Medicine of São Paulo University, 05403-000, São Paulo, Brazil

    • Marcelo Rubira
    • , Rodrigo Plentz
    • , Fernanda Consolim-Colombo
    •  & Maria Cláudia Irigoyen

Authors

  1. Search for Márcio Gonçalves de Sousa in:

  2. Search for Juan Carlos Yugar-Toledo in:

  3. Search for Marcelo Rubira in:

  4. Search for Sílvia Elaine Ferreira-Melo in:

  5. Search for Rodrigo Plentz in:

  6. Search for Deise Barbieri in:

  7. Search for Fernanda Consolim-Colombo in:

  8. Search for Maria Cláudia Irigoyen in:

  9. Search for Heitor Moreno in:

Corresponding author

Correspondence to Heitor Moreno Jr.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1111/j.1745-7254.2005.00069.x

Further reading