Traffic-related air pollution, stress, and sex: from inflammatory response to cardiovascular regulation in rats

Introduction: Epidemiological research shows that air pollution increases cardiovascular disease risk and is exacerbated by chronic stress exposure. However, the underlying mechanisms remain unknown. This study explored how traffic-related air pollution (TRAP) induced changes in inflammatory and oxidative stress markers, along with cardiovascular function, and the impact of stress. We hypothesized that chronic stress exacerbates TRAP-induced changes in cardiovascular regulation mechanistically through changes in inflammation. Methods: Adult Sprague Dawley rats (13 weeks old, both sexes) were exposed to real-time un-altered TRAP from the Caldecott tunnel in California for two weeks, with some receiving chronic mild unpredictable stress (CMUS) starting the week prior. At the end of each week, blood samples were collected from rats in each exposure group. Plasma cytokines and oxidative stress markers were determined using ELISA. Additional rats were implanted with a telemetry device to record blood pressure and electrocardiogram. Results: TRAP exposure significantly (p < 0.05) reduced some plasma cytokine levels (IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, G-CSF, M-CSF, IFN- γ, TNF-α) in male rats. Though not significant, we also saw a trend for TRAP exposure-induced increase in cytokine levels in female rats. CMUS exposure did not alter these results, suggesting a longer or stronger stress might be required to modify TRAP response, or that the TRAP effect was too large to see significance in the stress effect. Additionally, we saw no significant effect of TRAP, regardless of stress exposure, on C-reactive protein, 3-catalase level, and superoxide dismutase activity in either sex, suggesting no change in systemic oxidative stress levels. We also saw no effect on 24-hour blood pressure, pulse pressure, heart rate, or baroreflex sensitivity for either sex. However, female rats exposed to TRAP, regardless of stress exposure, had significantly (p < 0.05) lower SDANN (standard deviation of normal-to-normal RR interval) with no significant changes in rMSSD (root mean square of successive difference), suggesting a reduced autonomic regulation in the sympathetic limb. In male rats exposed to TRAP, we saw significantly (p < 0.05) lower left ventricular ejection fraction and fractional shortening, suggesting a reduced cardiac function. Conclusion: We uncovered significant sex differences in response to TRAP exposure, with stress as a modifier. In male rats, TRAP reduced cytokine production and cardiac mechanical function, both with and without CMUS exposure, suggesting a potential mechanistic role of inflammatory cytokines on cardiac function. In female rats, the consistent trend of elevated cytokine levels may contribute to a reduced sympathetic regulation. These findings could guide developing more biologically grounded epidemiologic model structures and refine the design of space-time exposure metrics for both stress and pollution. Support: R01ES033472-01A1 & P30 ES023513 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.