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.


OBJECTIVE
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.


CONCLUSIONS
Long-term CAPs exposure increases BP through sympathetic nervous system activation, which may involve hypothalamic inflammation.
Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
Zhekang
Z
Ying
Xiaohua
X
Xu
Yuntao
Y
Bai
Jixin
J
Zhong
Minjie
M
Chen
Yijia
Y
Liang
Jinzhuo
J
Zhao
Dongyao
D
Liu
Masako
M
Morishita
Qinghua
Q
Sun
Catherine
C
Spino
Robert D
RD
Brook
Jack R
JR
Harkema
Sanjay
S
Rajagopalan
D000393:Air Pollutants / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects* / Q000276:immunology*; D007249:Inflammation / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052638:Particulate Matter / Q000633:toxicity*; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000393:Air Pollutants; D052638:Particulate Matter