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Vascular Oxidative Stress Induced by Diesel Exhaust Microparticles: Synergism With Hypertension

Labranche, Nathalie PharmD*; El Khattabi, Charaf BSc*; Dewachter, Laurence PhD; Dreyfuss, Céline MD; Fontaine, Jeanine PhD*; van de Borne, Philippe MD, PhD; Berkenboom, Guy MD, PhD; Pochet, Stéphanie PhD*

Journal of Cardiovascular Pharmacology: December 2012 - Volume 60 - Issue 6 - p 530–537
doi: 10.1097/FJC.0b013e318270f1a8
Original Article

Background: Epidemiological and clinical studies have shown that traffic-related air pollution and, particularly, diesel exhaust particles (DEP) are strongly linked to cardiovascular mortality.

Methods: Vascular toxicity was studied by assessing vasomotor responses of aortas isolated from normotensive Wistar rats exposed in vitro to DEP (DEP suspension and aqueous DEP extract). In vivo experiments were performed on Wistar rats and spontaneously hypertensive rats (SHRs) exposed for 4 weeks via intratracheal instillation to either DEP or saline vehicle. After killing, vascular responses to acetylcholine (ACh) or sodium nitroprusside were assessed in vitro and the expression of p22phox, a major nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit, was studied by real-time quantitative polymerase chain reaction.

Results: In aortas from Wistar rats, in vitro DEP incubation (both preparations) markedly inhibited the relaxations to ACh and slightly to sodium nitroprusside; this effect was reversed in the presence of superoxide dismutase. In contrast, in aortas from in vivo–exposed animals, ACh-induced relaxations were only significantly impaired in the SHR group, accompanied with a significant upregulation of p22phox and no change in systolic blood pressure.

Conclusions: Although in vitro exposure to DEP produces a vascular oxidative stress, repeated in vivo exposures to DEP only impair vascular function in SHR, via an upregulation of p22phox. This suggests a synergistic effect on endothelial dysfunction between particulate air pollution and hypertension.

*Laboratory of Physiology and Pharmacology, Faculty of Pharmacy, Université Libre de Bruxelles, Bruxelles, Belgium

Laboratory of Physiology, Faculty of Medicine, Université Libre de Bruxelles, Bruxelles, Belgium

Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles, Bruxelles, Belgium.

Reprints: Nathalie Labranche, PharmD, Laboratory of Physiology and Pharmacology CP 205/7, Faculty of Pharmacy, Université Libre de Bruxelles, Campus Plaine, Blvd du Triomphe, B-1050 Bruxelles, Belgium (e-mail: Nathalie.Labranche@ulb.ac.be).

Supported by the “Fonds pour la Chirurgie Cardiaque” (G. Berkenboom), the “Fonds Docteur et Mme René Tagnon” (C. Dreyfuss), and “Fonds Erasme”, Erasme Hospital, Belgium (C. Dreyfuss). L. Dewachter is a postdoctoral fellow (Chargé de Recherche) from the “Fonds National de la Recherche Scientifique” (Belgium).

None of the funding sources intervened in any aspect of the study.

There are no conflicts of interest to declare.

Received June 14, 2012

Accepted August 24, 2012

© 2012 Lippincott Williams & Wilkins, Inc.