Long-Term Exposure to Concentrated Ambient PM2.5 Increases Mouse Blood Pressure through Abnormal Activation of the Sympathetic Nervous System: A Role for Hypothalamic Inflammation
Background: Exposure to particulate matter ≤ 2.5 μm in diameter (PM2.5) increases blood pressure (BP) in humans and animal models. Abnormal activation of the sympathetic nervous system may have a role in the acute BP response to PM2.5 exposure. The mechanisms responsible for sympathetic nervous system activation and its role in chronic sustenance of hypertension in response to PM2.5 exposure are currently unknown.
Objectives: We investigated whether central nervous system inflammation may be implicated in chronic PM2.5 exposure-induced increases in BP and sympathetic nervous system activation.
Methods: C57BL/6J mice were exposed to concentrated ambient PM2.5 (CAPs) for 6 months, and we analyzed BP using radioactive telemetric transmitters. We assessed sympathetic tone by measuring low-frequency BP variability (LF-BPV) and urinary norepinephrine excretion. We also tested the effects of acute pharmacologic inhibitors of the sympathetic nervous system and parasympathetic nervous system.
Results: Long-term CAPs exposure significantly increased basal BP, paralleled by increases in LF-BPV and urinary norepinephrine excretion. The increased basal BP was attenuated by the centrally acting α2a agonist guanfacine, suggesting a role of increased sympathetic tone in CAPs exposure–induced hypertension. The increase in sympathetic tone was accompanied by an inflammatory response in the arcuate nucleus of the hypothalamus, evidenced by increased expression of pro-inflammatory genes and inhibitor kappaB kinase (IKK)/nuclear factor–kappaB (NF-κB) pathway activation.
Conclusion: Long-term CAPs exposure increases BP through sympathetic nervous system activation, which may involve hypothalamic inflammation.
1Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, USA; 2Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, PR China; 3Division of Environmental Health Sciences, Colleges of Medicine and Public Health, The Ohio State University, Columbus, Ohio, USA; 4The University of Michigan, Ann Arbor, Michigan, USA; 5Michigan State University, East Lansing, Michigan, USA
Recommended Citation:
Zhekang Ying,1,2 Xiaohua Xu,et al. Long-Term Exposure to Concentrated Ambient PM2.5 Increases Mouse Blood Pressure through Abnormal Activation of the Sympathetic Nervous System: A Role for Hypothalamic Inflammation[J]. Environmental Health Perspectives,2014-01-01,Volume 122(Issue 1):79