Endothelial dysfunction in the pulmonary artery induced by concentrated fine particulate matter exposure is associated with local but not systemic inflammation

Author(s)

Davel, Ana Paula ^{[1, 2]} ; Lemos, Miriam ^[3] ; Pastro, Luciana Manfre ^[3] ; Pedro, Sibelli Cosme ^[3] ; de Andre, Paulo Afonso ^[4] ; Hebeda, Cristina ^[5] ; Farsky, Sandra Helena ^[5] ; Saldiva, Paulo Hilario ^[4] ; Rossoni, Luciana Venturini ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Dept Anat Cellular Biol Physiol & Biophys, Inst Biol, BR-13083865 Campinas, SP - Brazil

^[3] Univ Sao Paulo, Sch Med, Dept Surg, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

• Document type: Journal article
• Source: Toxicology; v. 295, n. 1-3, p. 39-46, MAY 16 2012.
• Web of Science Citations: 47

Abstract

Clinical evidence has identified the pulmonary circulation as an important target of air pollution. It was previously demonstrated that in vitro exposure to fine particulate matter (aerodynamic diameter <= 2.5 mu m, PM2.5) induces endothelial dysfunction in isolated pulmonary arteries. We aimed to investigate the effects of in vivo exposure to urban concentrated PM2.5 on rat pulmonary artery reactivity and the mechanisms involved. For this, adult Wistar rats were exposed to 2 weeks of concentrated Sao Paulo city air PM2.5 at an accumulated daily dose of approximately 600 mu g/m(3). Pulmonary arteries isolated from PM2.5-exposed animals exhibited impaired endothelium-dependent relaxation to acetylcholine without significant changes in nitric oxide donor response compared to control rats. PM2.5 caused vascular oxidative stress and enhanced protein expression of Cu/Zn- and Mn-superoxide dismutase in the pulmonary artery. Protein expression of endothelial nitric oxide synthase (eNOS) was reduced, while tumor necrosis factor (TNF)-alpha was enhanced by PM2.5 inhalation in pulmonary artery. There was a significant positive correlation between eNOS expression and maximal relaxation response (E-max) to acetylcholine. A negative correlation was found between vascular TNF-alpha expression and E-max to acetylcholine. Plasma cytokine levels, blood cells count and coagulation parameters were similar between control and PM2.5-exposed rats. The present findings showed that in vivo daily exposure to concentrated urban PM2.5 could decrease endothelium-dependent relaxation and eNOS expression on pulmonary arteries associated with local high TNF-alpha level but not systemic pro-inflammatory factors. Taken together, the present results elucidate the mechanisms underlying the trigger of cardiopulmonary diseases induced by urban ambient levels of PM2.5. (C) 2012 Elsevier Ireland Ltd. All rights reserved. (AU)

• FAPESP's process: 02/09804-0 - Pulmonary and cardiovascular alterations induced by inhalation of concentrated particulate material from the atmosphere of São Paulo
• Grantee: Paulo Hilário Nascimento Saldiva
• Support Opportunities: Regular Research Grants