Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease.

Aims: To investigate the existence of a relationship among flow-mediated dilation (FMD), nitric oxide (NO), and oxidative stress in patients with peripheral arterial disease (PAD), and to assess if the administration of an antioxidant was able to improve arterial dilatation.

Methods And Results: We performed a cross-sectional study comparing FMD, 8-Hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), a marker of oxidative stress, and nitrite/nitrate (NOx) serum levels in a population of 25 PAD patients and 40 controls. In the second part of the study, 21 PAD patients were randomly allocated to a treatment sequence of 7 days of i.v. infusion of placebo or 6 g/day propionyl-L-carnitine (PLC) in a cross-over design. Compared with controls, patients with PAD had enhanced 8-OHdG serum levels (2.4 +/- 1.2 vs. 4.24 +/- 3.11 ng/mL; P < 0.001), reduced NOx (17.02 +/- 6.11 vs. 11.28 +/- 6.02 microM; P < 0.001), and lowered FMD (10.34 +/- 2.14 vs. 6.69 +/- 2.95; P < 0.001). PLC infusion was associated with an increase of FMD [from 6.6 +/- 0.6 to 11.1 +/- 1.2% (mean +/- SE), P = 0.004] and NOx (from 14.5 +/- 1.4 to 17.1 +/- 1.2 microM; +18%, P = 0.012) and a decrease of 8-OHdG (from 3.62 +/- 0.37 to 2.64 +/- 0.32 ng/mL; -27%, P < 0.001). No changes were observed after placebo treatment.

Conclusion: This study shows that in PAD patients, oxidative stress is implicated in determining reduced FMD.