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

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 ≤2.5μm, 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 São Paulo city air PM₂.₅ at an accumulated daily dose of approximately 600μg/m³. 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)-α was enhanced by PM₂.₅ inhalation in pulmonary artery. There was a significant positive correlation between eNOS expression and maximal relaxation response (Eₘₐₓ) to acetylcholine. A negative correlation was found between vascular TNF-α expression and Eₘₐₓ 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-α 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.