Chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice
Authors: Pan Shiyue , Karey Emma , Nieves-Cintron Madeline , Chen Yi-Je (Jay) , Hwang Sung , Hammock Bruce , Pinkerton Kent , Chen Chao-Yin 
Published: May 2023

Background: Secondhand smoke (SHS) is a significant risk factor for cardiovascular morbidity and mortality. About 80% of SHS-related deaths are due to cardiovascular causes. Reducing SHS exposure with smoking bans is associated with improved cardiovascular outcomes in non-smokers. Soluble epoxide hydrolase (sEH) inhibitors have been shown to attenuate tobacco exposure-induced lung inflammatory responses, making them a great candidate for combating SHS exposure-induced cardiovascular outcomes. The goals of this study were to determine 1) the time course of environmentally relevant SHS exposure effects on cardiac autonomic function and blood pressure (BP) regulation and 2) whether prophylactic administration of a soluble epoxide hydrolase inhibitor (TPPU) can protect against SHS-induced autonomic and cardiovascular dysregulation. Methods: Male C57BL/6J mice (11 wk) implanted with BP/electrocardiogram (ECG) telemetry devices were exposed to 12 wks of either filtered air (FA, n=19) or 3 mg/m3 of SHS (6 hr/d, 5 d/wk, n=18), followed by 4 weeks recovery window (SHS substituted with FA). Separate mice were randomly assigned to one of the 3 groups: FA (n=12), FA+TPPU (n=12), and SHS+TPPU (n=22). TPPU (15 mg/l) was given by drinking water during the 12 weeks of exposure period (estimated dose = 3.75 ug/g/day). BP and ECG were recorded continuously for 36 hours every month when mice were not exposed. Data were stratified by 12-hour circadian window: The dark cycle (dark 1) immediately after the 5th day of exposure and the following light and dark (dark 2) cycles. Baroreflex sensitivity (BRS) was determined with the sequence method. Standard time domain heart rate variability (HRV) parameters were obtained from normal-to-normal R-R intervals. Results: SHS-exposed mice had significantly higher physical activity levels (~ 50% higher, p<0.05), an effect that persisted 4 wks after cessation of SHS exposure. SHS exposure significantly decreased 1) short-term HRV (RMSSD) by ~20% as early as after 4 wks of exposure; 2) overall HRV (SDNN) with maximum effect at 12 wks (-15%, p<0.05); 3) pulse pressure (-8%, p<0.05) as early as week 4; and 4) BRS with maximum effect at 12 wks (-11%, p<0.05). All SHS-induced changes in cardiovascular regulation were ameliorated by 4 weeks of recovery. Treatment with TPPU in drinking water eliminated SHS exposure-induced decreases in HRV, PP and BRS. However, SHS-induced increase in activity persisted (30% higher, p<0.05) even with TPPU treatment. Conclusions: These data suggest that 1) Three months of environmentally relevant SHS significantly reduces cardiac autonomic function and BP regulation; 2) cardiovascular consequences from SHS can be rescued by removing from SHS exposure; and 3) oral TPPU can prevent SHS-induced cardiovascular dysregulation. R01 ES025229, T32 HL086350, T32 ES007059, R35ES030443 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.