Aerobic training prevents the stress-induced endothelial dysfunction in male and female Wistar rats by different pathways

Variable stress contributes to cardiovascular morbidity by impairing endothelial function through oxidative stress, inflammation and hormonal imbalance. These effects depend on sex-specific physiological responses. While aerobic exercise is recognized for its vascular benefits, the mechanisms underlying these adaptations may differ between sexes. This study investigated the sex-specific effects of aerobic training on vascular function in Wistar rats subjected to variable stress. For this, male and female Wistar rats (n=8/group) were assigned to control or stress groups (8 days using four different types of stressor stimuli), with or without aerobic training (treadmill, moderate intensity, 30 min/day for 8 weeks). Thoracic aortic endothelial function was evaluated by acetylcholine-induced relaxation and phenylephrine-induced contraction. Antioxidant enzyme activity, nitrite concentration and protein expression of eNOS, p-eNOS ser1177 , catalase and superoxide dismutase were measured. Stress impaired endothelium-dependent relaxation and increased vascular collagen content in both sexes. In females, stress reduced eNOS phosphorylation and nitrite bioavailability, while increasing antioxidant enzyme activity. In males, no significant changes in the eNOS–NO pathway were observed, but SOD activity increased. Aerobic training attenuated stress-induced vascular injury, predominantly through the upregulation of the eNOS-NO signaling pathway in females, while in males, possibly through another pathway related to oxidative status. These findings demonstrate the protective effects of aerobic exercise on vascular health in rats subjected to variable stress and underscore the existence of sex-specific mechanisms, with distinct molecular pathways mediating vascular adaptations in males and females. Furthermore, histological analysis revealed that aerobic training reversed collagen deposition and enhanced elastic fiber content.