Effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice

Background: Secondhand smoke (SHS) is a significant risk factor for cardiovascular morbidity and mortality with an estimated 80% of SHS-related deaths attributed to cardiovascular causes. Public health measures and smoking bans have been successful both in reducing SHS exposure and improving cardiov...

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Main Authors: Shiyue Pan, Emma Karey, Madeline Nieves-Cintron, Yi-Je Chen, Sung Hee Hwang, Bruce D. Hammock, Kent E. Pinkerton, Chao-Yin Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2023.1185744/full
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author Shiyue Pan
Emma Karey
Madeline Nieves-Cintron
Yi-Je Chen
Sung Hee Hwang
Bruce D. Hammock
Kent E. Pinkerton
Chao-Yin Chen
author_facet Shiyue Pan
Emma Karey
Madeline Nieves-Cintron
Yi-Je Chen
Sung Hee Hwang
Bruce D. Hammock
Kent E. Pinkerton
Chao-Yin Chen
author_sort Shiyue Pan
collection DOAJ
description Background: Secondhand smoke (SHS) is a significant risk factor for cardiovascular morbidity and mortality with an estimated 80% of SHS-related deaths attributed to cardiovascular causes. Public health measures and smoking bans have been successful both in reducing SHS exposure and improving cardiovascular outcomes in non-smokers. Soluble epoxide hydrolase (sEH) inhibitors have been shown to attenuate tobacco exposure-induced lung inflammatory responses, making them a promising target for mitigating SHS exposure-induced cardiovascular outcomes.Objectives: The objectives of this study were to determine 1) effects of environmentally relevant SHS exposure on cardiac autonomic function and blood pressure (BP) regulation and 2) whether prophylactic administration of an sEH inhibitor (TPPU) can reduce the adverse cardiovascular effects of SHS exposure.Methods: Male C57BL/6J mice (11 weeks old) implanted with BP/electrocardiogram (ECG) telemetry devices were exposed to filtered air or 3 mg/m3 of SHS (6 hr/d, 5 d/wk) for 12 weeks, followed by 4 weeks of recovery in filtered air. Some mice received TPPU in drinking water (15 mg/L) throughout SHS exposure. BP, heart rate (HR), HR variability (HRV), baroreflex sensitivity (BRS), and BP variability were determined monthly.Results: SHS exposure significantly decreased 1) short-term HRV by ∼20% (p < 0.05) within 4 weeks; 2) overall HRV with maximum effect at 12 weeks (−15%, p < 0.05); 3) pulse pressure (−8%, p < 0.05) as early as week 4; and 4) BRS with maximum effect at 12 weeks (−11%, p < 0.05). Four weeks of recovery following 12 weeks of SHS ameliorated all SHS-induced cardiovascular detriments. Importantly, mice exposed to TPPU in drinking water during SHS-related exposure were protected from SHS cardiovascular consequences.Discussion: The data suggest that 1) environmental relevant SHS exposure significantly alters cardiac autonomic function and BP regulation; 2) cardiovascular consequences from SHS can be reversed by discontinuing SHS exposure; and 3) inhibiting sEH can prevent SHS-induced cardiovascular consequences.
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spelling doaj.art-2214c48644534fa8ada9d138c30b6cb52023-06-08T04:40:04ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-06-011410.3389/fphys.2023.11857441185744Effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in miceShiyue Pan0Emma Karey1Madeline Nieves-Cintron2Yi-Je Chen3Sung Hee Hwang4Bruce D. Hammock5Kent E. Pinkerton6Chao-Yin Chen7Department of Pharmacology, University of California Davis, Davis, CA, United StatesDepartment of Pharmacology, University of California Davis, Davis, CA, United StatesDepartment of Pharmacology, University of California Davis, Davis, CA, United StatesDepartment of Pharmacology, University of California Davis, Davis, CA, United StatesDepartment of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, United StatesDepartment of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, United StatesCenter for Health and the Environment, University of California Davis, Davis, CA, United StatesDepartment of Pharmacology, University of California Davis, Davis, CA, United StatesBackground: Secondhand smoke (SHS) is a significant risk factor for cardiovascular morbidity and mortality with an estimated 80% of SHS-related deaths attributed to cardiovascular causes. Public health measures and smoking bans have been successful both in reducing SHS exposure and improving cardiovascular outcomes in non-smokers. Soluble epoxide hydrolase (sEH) inhibitors have been shown to attenuate tobacco exposure-induced lung inflammatory responses, making them a promising target for mitigating SHS exposure-induced cardiovascular outcomes.Objectives: The objectives of this study were to determine 1) effects of environmentally relevant SHS exposure on cardiac autonomic function and blood pressure (BP) regulation and 2) whether prophylactic administration of an sEH inhibitor (TPPU) can reduce the adverse cardiovascular effects of SHS exposure.Methods: Male C57BL/6J mice (11 weeks old) implanted with BP/electrocardiogram (ECG) telemetry devices were exposed to filtered air or 3 mg/m3 of SHS (6 hr/d, 5 d/wk) for 12 weeks, followed by 4 weeks of recovery in filtered air. Some mice received TPPU in drinking water (15 mg/L) throughout SHS exposure. BP, heart rate (HR), HR variability (HRV), baroreflex sensitivity (BRS), and BP variability were determined monthly.Results: SHS exposure significantly decreased 1) short-term HRV by ∼20% (p < 0.05) within 4 weeks; 2) overall HRV with maximum effect at 12 weeks (−15%, p < 0.05); 3) pulse pressure (−8%, p < 0.05) as early as week 4; and 4) BRS with maximum effect at 12 weeks (−11%, p < 0.05). Four weeks of recovery following 12 weeks of SHS ameliorated all SHS-induced cardiovascular detriments. Importantly, mice exposed to TPPU in drinking water during SHS-related exposure were protected from SHS cardiovascular consequences.Discussion: The data suggest that 1) environmental relevant SHS exposure significantly alters cardiac autonomic function and BP regulation; 2) cardiovascular consequences from SHS can be reversed by discontinuing SHS exposure; and 3) inhibiting sEH can prevent SHS-induced cardiovascular consequences.https://www.frontiersin.org/articles/10.3389/fphys.2023.1185744/fullsidestream smokeautonomic functionbaroreflex sensitivitycardiovascular effectheart rate variabilitysoluble epoxide hydrolase
spellingShingle Shiyue Pan
Emma Karey
Madeline Nieves-Cintron
Yi-Je Chen
Sung Hee Hwang
Bruce D. Hammock
Kent E. Pinkerton
Chao-Yin Chen
Effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice
Frontiers in Physiology
sidestream smoke
autonomic function
baroreflex sensitivity
cardiovascular effect
heart rate variability
soluble epoxide hydrolase
title Effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice
title_full Effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice
title_fullStr Effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice
title_full_unstemmed Effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice
title_short Effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice
title_sort effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice
topic sidestream smoke
autonomic function
baroreflex sensitivity
cardiovascular effect
heart rate variability
soluble epoxide hydrolase
url https://www.frontiersin.org/articles/10.3389/fphys.2023.1185744/full
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