Impact of chronic exercise and ovarian hormones on resting sympathetic nerve activity and sympathetic transduction in female rats

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Elevated sympathetic nerve activity (SNA) and a sedentary lifestyle both increase the risk of cardiovascular diseases. During reproductive ages, women have lower SNA compared to age-matched men, suggesting a cardioprotective role of ovarian hormones. In contrast, our previous studies have shown that prepubertal female rats have enhanced increases in SNA compared to age-matched males, but similar pressor responses to centrally mediated sympathoexcitation, suggesting sex differences in SNA. However, whether the initial enhanced increases in SNA in females persist in the absence of the ovarian hormones or are further enhanced by sedentary conditions is unknown. Sympathetic transduction is a novel, robust method of assessing the physiological translation of SNA to blood pressure; however, it is unclear whether sympathetic transduction is ovarian hormone-dependent in female rodents. The goal of our study was to assess whether prepubertal ovariectomy alone or in combination with sedentary conditions increases resting SNA and sympathetic transduction in female rats. We hypothesized that both prepubertal ovariectomy and sedentary conditions contribute to increased resting SNA and sympathetic transduction compared to intact and physically active conditions. Prepubertal female Sprague-Dawley rats were ovariectomized (Ovx) or sham-operated (Sham) at 4 weeks of age and then randomized into a physically active (Active, running wheels) or sedentary group (Sed) for 12 weeks. Under Inactin anesthesia, baseline splanchnic SNA recordings were rectified and integrated in LabChart, while simultaneously recording beat-to-beat blood pressure. Using a customized Excel spreadsheet, sympathetic transduction to mean arterial pressure (MAP) was evaluated by signal averaging changes in MAP following a burst for the next 25 consecutive cardiac cycles. Sympathetic bursts were verified with thresholds derived after assessing SNA in the presence of full postganglionic blockade. Bursts were grouped according to pattern (Non-bursts, Single or Multiple bursts) and amplitude quartiles (Q1-Q4). Preliminary results are reported with n=3-5/group such that main effects were not always sufficiently powered to interpret p values above 0.05, but p values below 0.05 are reported. Resting sympathetic burst frequency (Freq, burst/min) appeared to be highest in Ovx-Sed (127 ± 27) compared to Sham-Sed (118 ± 36), Ovx-Active (100 ± 20), and Sham-Active (72 ± 29). Similarly, resting MAP (mmHg) appeared to be highest in Ovx groups compared to sham-operated groups. Multiple burst patterns had higher peak MAP transduction compared to non-bursts across all groups (p=0.002 main effect). Lastly, across all groups, bursts of the highest amplitudes (Q4) resulted in greater peak MAP transduction compared to bursts of the lowest amplitudes (Q1) (p=0.043 main effect). Transduction in Q1 vs Q4 amplitudes (mmHg) appeared highest in Ovx-Sed (0.33 ± 0.24 vs 1.01 ± 0.52) compared to Sham-Sed (0.24 ± 0.09 vs 0.53 ± 0.18), Ovx-Active (0.20 ± 0.12 vs 0.54 ± 0.23), and Sham-Active (0.15 ± 0.06 vs 0.47 ± 0.14). Our preliminary results illustrate a possibility of increased baseline SNA and sympathetic transduction in sedentary females ovariectomized prior to puberty, but further studies are needed to confirm our hypothesis. Our results also suggest that ovarian hormones confer additional cardioprotection from opposing prepubertal sex differences via reduced SNA and sympathetic transduction regardless of physical activity. R01HL161233 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.

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