Air pollution exposure potentiates hypertension through reactive oxygen species-mediated activation of Rho/ROCK

Qinghua Sun; Peibin Yue; Zhekang Ying; Arturo J. Cardounel; Robert D. Brook; Robert Devlin; Jing Shiang Hwang; Jay L. Zweier; Chi Chen Lung; Sanjay Rajagopalan

doi:10.1161/ATVBAHA.108.166967

Air pollution exposure potentiates hypertension through reactive oxygen species-mediated activation of Rho/ROCK

Qinghua Sun, Peibin Yue, Zhekang Ying, Arturo J. Cardounel, Robert D. Brook, Robert Devlin, Jing Shiang Hwang, Jay L. Zweier, Chi Chen Lung, Sanjay Rajagopalan

Research output: Contribution to journal › Article › peer-review

155 Scopus citations

Abstract

Objective - Fine particulate matter 2.5) has been implicated in vasoconstriction and potentiation of hypertension in humans. We investigated the effects of short-term exposure to PM_2.5 in the angiotensin II (AII) infusion model. Methods and Results - Sprague-Dawley rats were exposed to PM_2.5 or filtered air (FA) for 10 weeks. At week 9, minipumps containing AII were implanted and the responses studied over a week. Mean concentration of PM_2.5 inside the chamber was 79.1±7.4 μg/m³. After All infusion, mean arterial pressure was significantly higher in PM_2.5-AII versus FA-AII group. Aortic vasoconstriction to phenylephrine was potentiated with exaggerated relaxation to the Rho-kinase (ROCK) inhibitor Y-27632 and increase in ROCK-1 mRNA levels in the PM_2.5-AII group. Superoxide (O₂^.-) production in aorta was increased in the PM^2.5-AII compared to the FA group, inhibitable by apocynin and L-NAME with coordinate upregulation of NAD(P)H oxidase subunits p22^phox and p47^phox and depletion of tetrahydrobiopterin. In vitro exposure to ultrafine particles (UFP) and PM_2.5 was associated with an increase in ROCK activity, phosphorylation of myosin light chain, and myosin phosphatase target subunit (MYPT1). Pretreatment with the nonspecific antioxidant N-Acetylcysteine and the Rho kinase inhibitors (Fasudil and Y-27632) prevented MLC and MYPT-1 phosphorylation by UFP suggesting a O₂^.--mediated mechanism for PM_2.5 and UFP effects. Conclusions - Short-term air pollution exaggerates hypertension through O₂^.--mediated upregulation of the Rho/ROCK pathway.

Original language	English (US)
Pages (from-to)	1760-1766
Number of pages	7
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	28
Issue number	10
DOIs	https://doi.org/10.1161/ATVBAHA.108.166967
State	Published - Oct 2008
Externally published	Yes

Keywords

Air pollution
Free radicals
Hypertension
NADPH oxidase
Rho/ROCK

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1161/ATVBAHA.108.166967

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@article{dba92c86592c4ecd81c741c6ce9edc75,

title = "Air pollution exposure potentiates hypertension through reactive oxygen species-mediated activation of Rho/ROCK",

abstract = "Objective - Fine particulate matter 2.5) has been implicated in vasoconstriction and potentiation of hypertension in humans. We investigated the effects of short-term exposure to PM2.5 in the angiotensin II (AII) infusion model. Methods and Results - Sprague-Dawley rats were exposed to PM2.5 or filtered air (FA) for 10 weeks. At week 9, minipumps containing AII were implanted and the responses studied over a week. Mean concentration of PM2.5 inside the chamber was 79.1±7.4 μg/m3. After All infusion, mean arterial pressure was significantly higher in PM2.5-AII versus FA-AII group. Aortic vasoconstriction to phenylephrine was potentiated with exaggerated relaxation to the Rho-kinase (ROCK) inhibitor Y-27632 and increase in ROCK-1 mRNA levels in the PM2.5-AII group. Superoxide (O2.-) production in aorta was increased in the PM2.5-AII compared to the FA group, inhibitable by apocynin and L-NAME with coordinate upregulation of NAD(P)H oxidase subunits p22phox and p47phox and depletion of tetrahydrobiopterin. In vitro exposure to ultrafine particles (UFP) and PM2.5 was associated with an increase in ROCK activity, phosphorylation of myosin light chain, and myosin phosphatase target subunit (MYPT1). Pretreatment with the nonspecific antioxidant N-Acetylcysteine and the Rho kinase inhibitors (Fasudil and Y-27632) prevented MLC and MYPT-1 phosphorylation by UFP suggesting a O2.--mediated mechanism for PM2.5 and UFP effects. Conclusions - Short-term air pollution exaggerates hypertension through O2.--mediated upregulation of the Rho/ROCK pathway.",

keywords = "Air pollution, Free radicals, Hypertension, NADPH oxidase, Rho/ROCK",

author = "Qinghua Sun and Peibin Yue and Zhekang Ying and Cardounel, {Arturo J.} and Brook, {Robert D.} and Robert Devlin and Hwang, {Jing Shiang} and Zweier, {Jay L.} and Lung, {Chi Chen} and Sanjay Rajagopalan",

year = "2008",

month = oct,

doi = "10.1161/ATVBAHA.108.166967",

language = "English (US)",

volume = "28",

pages = "1760--1766",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams and Wilkins",

number = "10",

}

TY - JOUR

T1 - Air pollution exposure potentiates hypertension through reactive oxygen species-mediated activation of Rho/ROCK

AU - Sun, Qinghua

AU - Yue, Peibin

AU - Ying, Zhekang

AU - Cardounel, Arturo J.

AU - Brook, Robert D.

AU - Devlin, Robert

AU - Hwang, Jing Shiang

AU - Zweier, Jay L.

AU - Lung, Chi Chen

AU - Rajagopalan, Sanjay

PY - 2008/10

Y1 - 2008/10

N2 - Objective - Fine particulate matter 2.5) has been implicated in vasoconstriction and potentiation of hypertension in humans. We investigated the effects of short-term exposure to PM2.5 in the angiotensin II (AII) infusion model. Methods and Results - Sprague-Dawley rats were exposed to PM2.5 or filtered air (FA) for 10 weeks. At week 9, minipumps containing AII were implanted and the responses studied over a week. Mean concentration of PM2.5 inside the chamber was 79.1±7.4 μg/m3. After All infusion, mean arterial pressure was significantly higher in PM2.5-AII versus FA-AII group. Aortic vasoconstriction to phenylephrine was potentiated with exaggerated relaxation to the Rho-kinase (ROCK) inhibitor Y-27632 and increase in ROCK-1 mRNA levels in the PM2.5-AII group. Superoxide (O2.-) production in aorta was increased in the PM2.5-AII compared to the FA group, inhibitable by apocynin and L-NAME with coordinate upregulation of NAD(P)H oxidase subunits p22phox and p47phox and depletion of tetrahydrobiopterin. In vitro exposure to ultrafine particles (UFP) and PM2.5 was associated with an increase in ROCK activity, phosphorylation of myosin light chain, and myosin phosphatase target subunit (MYPT1). Pretreatment with the nonspecific antioxidant N-Acetylcysteine and the Rho kinase inhibitors (Fasudil and Y-27632) prevented MLC and MYPT-1 phosphorylation by UFP suggesting a O2.--mediated mechanism for PM2.5 and UFP effects. Conclusions - Short-term air pollution exaggerates hypertension through O2.--mediated upregulation of the Rho/ROCK pathway.

AB - Objective - Fine particulate matter 2.5) has been implicated in vasoconstriction and potentiation of hypertension in humans. We investigated the effects of short-term exposure to PM2.5 in the angiotensin II (AII) infusion model. Methods and Results - Sprague-Dawley rats were exposed to PM2.5 or filtered air (FA) for 10 weeks. At week 9, minipumps containing AII were implanted and the responses studied over a week. Mean concentration of PM2.5 inside the chamber was 79.1±7.4 μg/m3. After All infusion, mean arterial pressure was significantly higher in PM2.5-AII versus FA-AII group. Aortic vasoconstriction to phenylephrine was potentiated with exaggerated relaxation to the Rho-kinase (ROCK) inhibitor Y-27632 and increase in ROCK-1 mRNA levels in the PM2.5-AII group. Superoxide (O2.-) production in aorta was increased in the PM2.5-AII compared to the FA group, inhibitable by apocynin and L-NAME with coordinate upregulation of NAD(P)H oxidase subunits p22phox and p47phox and depletion of tetrahydrobiopterin. In vitro exposure to ultrafine particles (UFP) and PM2.5 was associated with an increase in ROCK activity, phosphorylation of myosin light chain, and myosin phosphatase target subunit (MYPT1). Pretreatment with the nonspecific antioxidant N-Acetylcysteine and the Rho kinase inhibitors (Fasudil and Y-27632) prevented MLC and MYPT-1 phosphorylation by UFP suggesting a O2.--mediated mechanism for PM2.5 and UFP effects. Conclusions - Short-term air pollution exaggerates hypertension through O2.--mediated upregulation of the Rho/ROCK pathway.

KW - Air pollution

KW - Free radicals

KW - Hypertension

KW - NADPH oxidase

KW - Rho/ROCK

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U2 - 10.1161/ATVBAHA.108.166967

DO - 10.1161/ATVBAHA.108.166967

M3 - Article

C2 - 18599801

AN - SCOPUS:53449083967

SN - 1079-5642

VL - 28

SP - 1760

EP - 1766

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

IS - 10

ER -

Air pollution exposure potentiates hypertension through reactive oxygen species-mediated activation of Rho/ROCK

Abstract

Keywords

ASJC Scopus subject areas

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