Lower extremity peripheral artery disease (PAD), due to narrowing of the arteries supplying the legs, represents a major cause of physical disability. Moderate-intensity exercise training (MICT) is an important part of PAD treatment, improving functional capacity. Recent research suggests that exercise training-induced endothelial function improvement is involved in the benefits of exercise in PAD; however, the underlying mechanisms remain unknown. High-intensity interval training (HIIT) has been shown to be an effective alternative to MICT but its potential vascular benefits of in PAD remain unexplored. The aim of this study was therefore to compare the effects of MICT and HIIT on endurance capacity, vascular reactivity, and vascular/systemic bioavailability of nitric oxide (NO) in a mouse model of PAD.

PAD disease model was generated in male C57BL/6 mice by ligation of the right iliac artery. Mice were then divided into 3 groups: sedentary control group (SED), MICT and HIIT. Mice were exercised three times per week for 8 weeks. Maximal running time was determined by an incremental test until exhaustion. Vascular reactivity was assessed in isolated aortic rings. Gene and/or protein expression of enzymes involved in NO bioavailability and in pro/antioxidant balance was determined in aortic tissue by qPCR and Western blot, respectively. NO metabolites and markers of pro/antioxidant balance were measured in plasma by spectrophotometry.

Maximal running time was improved in both MICT and HIIT as compared to SED at the end of the study), but with no significant difference between the two exercise groups. Endothelium-dependent and -independent vasodilator responses to acetylcholine and DEA-NONOate, respectively, were improved in MICT compared to SED while no significant differences were reported between HIIT and SED. There was no significant difference in gene and/or protein expression of eNOS, NADPH oxidase p22phox and p47phox subunits and superoxide dismutase isoforms 1 and 2 among the three groups. Plasma total nitrite and nitrate did not significantly differ among the three groups while nitrotyrosine was higher in MICT as compared to SED.

MICT and HIIT are equally effective at improving endurance capacity in mice with PAD. However, only MICT improves vascular endothelial function. MICT and HIIT do not appear to modulate NO bioavailability in our mouse model.