Vitamins C and E Inhibit O 2 − Production in the Pig Coronary Artery

Abstract

Background We previously found in a pig coronary balloon injury model that vitamins C and E as well as probucol had beneficial effects on the vessel response to injury measured by morphometry _. These effects correlated with an inhibition in the ability to oxidize LDLs ex vivo, suggesting that the morphological response was due to the antioxidant effect of the treatments. Methods and Results In the present study, the production of O ₂ ⁻ by vessels 14 days after balloon injury was determined and correlated with circulating and tissue levels of vitamins C and E. Twenty-five domestic pigs were divided into four groups: control (n=7), vitamin C (500 mg/d, group C, n=6), vitamin E (1000 IU/d, group E, n=6), and vitamins C and E (500 mg/d and 1000 IU/d, group C+E, n=6). Vitamins were administered 7 days before oversized balloon injury of the left anterior descending coronary artery (LAD) and continued for 14 days after injury. Vitamin C and E concentrations were determined in plasma and lymphocytes as an index for tissue levels. Vessels were harvested after animals were killed, and O ₂ ⁻ production was measured by lucigenin chemiluminescence. O ₂ ⁻ production by the injured LAD was 2.5-fold greater than O ₂ ⁻ production by the uninjured LAD or right coronary artery (RCA). The increase in O ₂ ⁻ was caused primarily by cells present in the media and neointima. All vitamin-treated groups showed significantly decreased O ₂ ⁻ production in both the RCA and LAD (≈45% inhibition) relative to vessels in the control, untreated group. There was a significant correlation between LAD O ₂ ⁻ production and lymphocyte vitamin E levels. Conclusions The present study is the first to show increased O ₂ ⁻ production in injured vessels and to demonstrate that antioxidant vitamins reduce O ₂ ⁻ production. These results suggest that beneficial effects of antioxidant vitamins in coronary artery disease are related, in part, to alterations in vessel redox state.