Hormone–exercise interactions in renal oxidative stress and vascular signaling pathways of female rats

Regular physical activity is an effective strategy to improve health and reduce the risk of chronic disease, including chronic kidney disease, hypertension and more serious cardiovascular disease. The physiological benefits of exercise are influenced by biological sex, with recent evidence showing ovarian hormones play a critical role in modulating these responses. Oxidative stress and vascular pathways are key mediators of exercise adaptations in the periphery. p67PHOX, a subunit of NADPH oxidase, contributes to reactive oxygen species production, while antioxidant defenses including MnSOD counteract oxidative stress. Additionally, eNOS and AT1R regulate vascular tone and blood pressure through nitric oxide and angiotensin II signaling, respectively. In this study, female rats underwent either sham surgery or ovariectomy (OVX) and, following recovery from surgery, were randomly assigned to sedentary or voluntary wheel running (VWR) conditions for approximately 6 weeks. RNA was extracted from renal cortex and medulla samples, converted to cDNA, and analyzed by qPCR to assess the gene expression of oxidative stress and vascular markers. p67PHOX was elevated in the renal medulla of rats that underwent OVX; VWR tended to decrease the expression of p67PHOX in the medulla. MnSOD decreased in the renal cortex of rats that underwent OVX but was unchanged by VWR. AT1R gene expression increased in the renal medulla of rats that underwent OVX but was unaffected by VWR status. eNOS expression was increased in the renal cortex of sham-operated rats with VWR access. In OVX-operated animals, eNOS gene expression was increased vs. sham in the renal cortex; VWR access tended to reduce the expression of eNOS in the OVX-operated animals. These findings highlight region-specific hormone–exercise interactions and support development of sex-specific strategies targeting redox and vascular tone to optimize health outcomes. Further analysis will determine if exercise activity correlates with the expression of these targets and we anticipate a strong correlation between activity level and expression for eNOS. These findings will allow us to untangle the influence of exercise behavior and hormone status to better understand the complex interplay between these variables. FUNDING SOURCE: internal DMU funding, AHA 24TPA1298609 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.