Impaired plasma nitric oxide availability and extracellular superoxide dismutase activity in healthy humans with advancing age

This study is aimed to verify the modifications of extracellular superoxide dismutase (EC-SOD) activity and its potential involvement on the mechanism responsible for the impairment of plasma nitric oxide (NO) availability occurring with advancing age in healthy humans. For this purpose, plasma samples were drawn from 40 healthy men, aged 20-92 years, in fasting state and used for measurements of stable end-product nitrite/nitrate (NOx), as expression of NO availability, EC-SOD activity, thiobarbituric acid reactive substances (TBARS) as marker of lipid peroxidation, Trolox equivalent antioxidant capacity (TEAC) as a measure of plasma total antioxidant capacity, and in vitro susceptibility of low density lipoprotein (LDL) to copper-mediated oxidation, evaluated as lag time. As indicated by our results, advancing age was significantly related to decreased plasma values of NOx (r = -0.877, P < 0.001), EC-SOD activity (r = -0.888, P < 0.001), TEAC (r = -0.647, P < 0.001) and lag time (r = -0.621, P < 0.001) as well as to an increased plasma amount of TBARS (r = 0.858, P < 0.001). NOx plasma level resulted independently predicted by EC-SOD activity and age. EC-SOD activity, in turn, was determined by age and TEAC. Taken together, findings of the present study give further insight into the mechanism related to age-associated endothelial dysfunction, indicating that the decreased EC-SOD activity may be involved in the progressive reduction of plasma NO availability with advancing age through the age-related impairment of oxidant/antioxidant balance.