Author(s): KOJIC, S., MENÉTREY, S., ROSENBLATT-VELIN, N., MAZZOLAI, L., PEYTER, A.N., MILLET, G., PELLEGRIN, M., Institution: UNIVERSITY OF LAUSANNE, Country: SWITZERLAND, Abstract-ID: 1902

INTRODUCTION:
Lower extremity peripheral artery disease (PAD) is characterized by arterial narrowing and is associated with increased cardiovascular morbidity and mortality. The endothelium, a key regulator of vascular homeostasis, represents a major therapeutic target for reducing cardiovascular risk. Exercise training is a cornerstone of PAD management, and accumulating evidence suggests that improvements in endothelial function contribute to its clinical benefits. However, the molecular mechanisms underlying these adaptations remain poorly understood. In addition, the vascular effects of high-intensity exercise in PAD remain unexplored. This study compared the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on vascular function and markers involved in nitric oxide (NO) bioavailability in a murine model of PAD.
METHODS:
PAD was induced in male C57BL/6 mice by right iliac artery ligation. Animals were allocated to three groups: sedentary control (SED), MICT (40 min running at 70% maximal aerobic speed [MAS]), or HIIT (8 x 2.5 min at 90% MAS interspersed with 2.5 min at 50% MAS). Training was performed three times per week for 8 weeks. Vascular reactivity was assessed in isolated aortic rings using phenylephrine-induced vasoconstriction and acetylcholine- and DEA-NONOate-induced vasodilatation (endothelium-dependent and -independent, respectively). Aortic expression of antioxidant enzymes (catalase, SOD isoforms), pro-oxidant NADPH oxidase subunits (p22phox, p47phox), endothelial NO synthase (eNOS), soluble guanylate cyclase (sGC), and adrenergic receptors (a1 and b2) was assessed by qPCR and/or Western blot.
RESULTS:
Both endothelium-dependent and endothelium-independent vasodilation, as well as phenylephrine-induced vasoconstriction, were significantly improved in the MICT group compared with SED (p < 0.05). In contrast, no significant differences in vascular reactivity were observed between the HIIT and SED groups. No significant differences were observed between groups in the expression of markers related to oxidative stress or NO bioavailability at the mRNA or protein levels.
CONCLUSION:
MICT, but not HIIT, significantly improves vascular reactivity in a murine model of PAD. These findings highlight exercise intensity as a critical determinant of vascular adaptation in PAD and suggest that the vascular benefits of moderate-intensity exercise occur through mechanisms independent of classical NO-related pathways.