Effect of ascorbic acid on endothelial dysfunction of epicardial coronary arteries in chronic smokers assessed by cold pressor testing

Cardiology. 2000;94(4):239-46. doi: 10.1159/000047324.


Background: In chronic smokers there is evidence for increased formation of oxygen-derived free radicals within the vessel wall impairing endothelial function. It has been suggested that the inactivation of endothelium-derived nitric oxide by oxygen free radicals contributes to endothelial dysfunction. Hence, we tested the hypothesis that in chronic smokers the antioxidant ascorbic acid could improve abnormal endothelial function of epicardial coronary arteries.

Methods and results: Thirty-one patients (mean age 57 +/- 9 years) referred for routine diagnostic catheterization for evaluation of chest pain and without angiographically significant coronary artery stenoses were randomly assigned to one of the study groups to assess vasomotor response of epicardial coronary arteries due to cold pressor testing (CPT) before and after intravenous infusion of 3 g of ascorbic acid or 100 ml x 0.9% saline infusion. In 6 controls (mean age 55 +/- 3 years) CPT led to a similar increase in luminal area before and after ascorbic acid administration (26.5 +/- 15.0 vs. 28.4 +/- 17.7%, p = NS). In 15 chronic smokers (mean age 55 +/- 9 years), CPT induced a decrease in the luminal area of -18.5 +/- 6.3%. This flow-dependent vasoconstriction was significantly reversed to 7.7 +/- 6.2% (p < or = 0.03) vasodilation after intravenous ascorbic acid administration. In 10 chronic smokers (mean age 57 +/- 11 years) saline infusion (placebo) did not have a significant effect on CPT-induced vasoconstriction (-12.7 +/- 5.1 vs. -13.1 +/- 5.1%, p = NS). The CPT-induced increase in luminal area in chronic smokers after ascorbic acid infusion was significant compared to controls and placebo (each p < or = 0.05). Our assessment of endothelium-independent responses to nitroglycerin revealed no significant differences between the single study groups (p = NS).

Conclusion: In chronic smokers acute intravenous administration of ascorbic acid significantly improves CPT-induced coronary endothelium-dependent dysfunction. According to the current understanding, this effect is due to improved cellular redox imbalance and prevention of nitric oxide inactivation in the endothelium and subendothelial space.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antioxidants / pharmacology*
  • Ascorbic Acid / analysis
  • Ascorbic Acid / pharmacology
  • Blood Pressure / physiology*
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cold Temperature*
  • Coronary Vessels / drug effects*
  • Double-Blind Method
  • Endothelium, Vascular / drug effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitroglycerin / pharmacology
  • Prospective Studies
  • Smoking / adverse effects*
  • Vasoconstriction / drug effects
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology


  • Antioxidants
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Vasodilator Agents
  • Cholesterol
  • Nitroglycerin
  • Ascorbic Acid