This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 28/10/1760    most recent ATVBAHA.108.166967v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sun, Q. Articles by Rajagopalan, S. Search for Related Content PubMed PubMed Citation Articles by Sun, Q. Articles by Rajagopalan, S. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1760.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

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; Lung Chi Chen; Sanjay Rajagopalan

From the Davis Heart Lung Research Institute (Q.S., P.Y., Z.Y., A.J.C., J.L.Z., S.R.) and the Division of Environmental Health Sciences (Q.S.), Colleges of Medicine and Public Health, The Ohio State University, Columbus; the Department of Internal Medicine (R.D.B.), University of Michigan, Ann Arbor; the US Environmental Protection Agency (R.D.), Research Triangle Park, NC; the Institute of Statistical Science (J.-S.H.), Academia Sinica, Taipei, Taiwan and the Department of Environmental Medicine and Nelson Institute of Environmental Medicine (L.C.C.), New York University School of Medicine.

Correspondence to Sanjay Rajagopalan, MD, Wolfe Professor of Medicine and Radiology, Davis Heart Lung Research Institute, Room 110, 473 W 12th Avenue, Columbus, OH 43210-1252. E-mail sanjay.rajagopalan{at}osumc.edu

Objective— Fine particulate matter <2.5 µm (PM_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 AII 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.

Short-term exposure to ambient fine particles in an angiotensin II rat model exaggerates vasoconstriction and blood pressure through increases in vascular superoxide production and upregulation of the Rho/ROCK pathway.

Key Words: air pollution • NADPH oxidase • hypertension • free radicals • Rho/ROCK

This article has been cited by other articles:

				Z. Ying, T. Kampfrath, G. Thurston, B. Farrar, M. Lippmann, A. Wang, Q. Sun, L. C. Chen, and S. Rajagopalan Ambient Particulates Alter Vascular Function through Induction of Reactive Oxygen and Nitrogen Species Toxicol. Sci., September 1, 2009; 111(1): 80 - 88. [Abstract] [Full Text] [PDF]

				T. R. Nurkiewicz, D. W. Porter, A. F. Hubbs, S. Stone, B. T. Chen, D. G. Frazer, M. A. Boegehold, and V. Castranova Pulmonary Nanoparticle Exposure Disrupts Systemic Microvascular Nitric Oxide Signaling Toxicol. Sci., July 1, 2009; 110(1): 191 - 203. [Abstract] [Full Text] [PDF]

				Z. Ying, P. Yue, X. Xu, M. Zhong, Q. Sun, M. Mikolaj, A. Wang, R. D. Brook, L. C. Chen, and S. Rajagopalan Air pollution and cardiac remodeling: a role for RhoA/Rho-kinase Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1540 - H1550. [Abstract] [Full Text] [PDF]

				A. K. Hamade and C. G. Tankersley Interstrain variation in cardiac and respiratory adaptation to repeated ozone and particulate matter exposures Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R1202 - R1215. [Abstract] [Full Text] [PDF]

				P. P. Ongusaha, H. H. Qi, L. Raj, Y.-B. Kim, S. A. Aaronson, R. J. Davis, Y. Shi, J. K. Liao, and S. W. Lee Identification of ROCK1 as an Upstream Activator of the JIP-3 to JNK Signaling Axis in Response to UVB Damage Sci. Signal., November 25, 2008; 1(47): ra14 - ra14. [Abstract] [Full Text] [PDF]