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

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-derive d nitric oxide by oxygen free radicals contributes to endothelial dysfuncti on. Hence, we tested the hypothesis that in chronic smokers the antioxidant ascorbic acid could improve abnormal endothelial function of epicardial co ronary 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 stenose s were randomly assigned to one of the study groups to assess vasomotor res ponse of epicardial coronary arteries due to cold presser testing (CPT) bef ore and after intravenous infusion of 3 g of ascorbic acid or 100 mi x 0.9% saline infusion, In 6 controls (mean age 55 +/- 3 years) CPT led to a simi lar 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 less than or equal to 0.03) vasodilation after intravenous asc orbic 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 induc ed increase in luminal area in chronic smokers after ascorbic acid infusion was significant compared to controls and placebo (each p less than or equa l to 0.05). Our assessment of endothelium-independent responses to nitrogly cerin 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-depe ndent dysfunction. According to the current understanding, this effect is d ue to improved cellular redox imbalance and prevention of nitric oxide inac tivation in the endothelium and subendothelial space. Copyright (C) 2001 S. Karger AG, Basel.