Pollutant particles produce vasoconstriction and enhance MAPK signaling via angiotensin type I receptor.
Abstract
Exposure to particulate matter (PM) is associated with acute cardiovascular mortality
and morbidity, but the mechanisms are not entirely clear. In this study, we hypothesized
that PM may activate the angiotensin type 1 receptor (AT1R), a G protein-coupled receptor
that regulates inflammation and vascular function. We investigated the acute effects
of St. Louis, Missouri, urban particles (UPs; Standard Reference Material 1648) on
the constriction of isolated rat pulmonary artery rings and the activation of extracellular
signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinases
(MAPKs) in human pulmonary artery endothelial cells with or without losartan, an antagonist
of AT1R. UPs at 1-100 microg/mL induced acute vasoconstriction in pulmonary artery.
UPs also produced a time- and dose-dependent increase in phosphorylation of ERK1/2
and p38 MAPK. Losartan pretreatment inhibited both the vasoconstriction and the activation
of ERK1/2 and p38. The water-soluble fraction of UPs was sufficient for inducing ERK1/2
and p38 phosphorylation, which was also losartan inhibitable. Copper and vanadium,
two soluble transition metals contained in UPs, induced pulmonary vasoconstriction
and phosphorylation of ERK1/2 and p38, but only the phosphorylation of p38 was inhibited
by losartan. The UP-induced activation of ERK1/2 and p38 was attenuated by captopril,
an angiotensin-converting enzyme inhibitor. These results indicate that activation
of the local renin-angiotensin system may play an important role in cardiovascular
effects induced by PM.
Type
Journal articleSubject
Pulmonary ArteryCells, Cultured
Endothelial Cells
Animals
Humans
Rats
Rats, Sprague-Dawley
Copper
Vanadium
Losartan
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
p38 Mitogen-Activated Protein Kinases
Receptor, Angiotensin, Type 1
Dust
Air Pollutants
Cities
Air Pollution
Phosphorylation
Vasoconstriction
Particle Size
Missouri
In Vitro Techniques
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https://hdl.handle.net/10161/22251Published Version (Please cite this version)
10.1289/ehp.7736Publication Info
Li, Zhuowei; Carter, Jacqueline D; Dailey, Lisa A; & Huang, Yuh-Chin T (2005). Pollutant particles produce vasoconstriction and enhance MAPK signaling via angiotensin
type I receptor. Environmental health perspectives, 113(8). pp. 1009-1014. 10.1289/ehp.7736. Retrieved from https://hdl.handle.net/10161/22251.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Yuh-Chin Tony Huang
Professor of Medicine
Closed loop ventilation Environmental medicine Oxidative lung injuryCOPDHyperpolarized
129Xe MRI and regional lung function

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