Exercise Improves Endothelium-Dependent H₂S-Mediated Vasodilation in Ovariectomized Rats via a COX-Dependent Mechanism

17β-estradiol (E2) stimulates the production of nitric oxide (NO) and hydrogen sulfide (H₂S). Although physical exercise effectively enhances NO-mediated vasodilation under estrogen-deficient conditions, the role of H₂S in this context is not yet fully understood. We investigated the effect of exercise on H₂S-mediated dilation in the thoracic aorta of ovariectomized rats. Female Wistar rats were randomly divided into the following groups: Sham + Sedentary (SS), Sham + Exercise (SE), Ovariectomy + Sedentary (OS), and Ovariectomy + Exercise (OE). After eight weeks of exercise, vascular reactivity was assessed. NO and superoxide anion were measured using DAF-2 and DHE probes, respectively. The OS group showed reduced H₂S-mediated vasodilation; however, this response was significantly improved after exercise. Sodium hydrosulfide (NaHS) produced similar effects on vascular reactivity. Endothelial removal abolished the differences in exercise-induced improvement in H₂S-mediated vasodilation. In addition, inhibition of NO synthesis did not prevent the exercise-induced enhancement of H₂S-mediated vasodilation in the OS and OE groups, indicating a NO-independent mechanism. In contrast, cyclooxygenase (COX) inhibition abolished the exercise-induced improvement in H₂S-mediated vasodilation. Exercise also increased NO production and reduced superoxide anion generation. Our results demonstrate that exercise improves endothelium-dependent vasodilation through H₂S formation via a COX-dependent mechanism in ovariectomized rats.