Open Access Research

Cardiovascular and inflammatory effects of intratracheally instilled ambient dust from Augsburg, Germany, in spontaneously hypertensive rats (SHRs)

Swapna Upadhyay1, Koustav Ganguly1, Tobias Stoeger1, Manuela Semmler-Bhenke1, Shinji Takenaka1, Wolfgang G Kreyling12, Mike Pitz3, Peter Reitmeir4, Annette Peters3, Oliver Eickelberg1, H Erich Wichmann23 and Holger Schulz12*

Author Affiliations

1 Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, D85764, Neuherberg/Munich, Germany

2 Focus Network Nanoparticles and Health, German Research Center for Environmental Health, Neuherberg, Germany. Ingolstaedter Landstrasse 1, D85764, Neuherberg/Munich, Germany

3 Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, D85764, Neuherberg/Munich, Germany

4 Institute of Health Economics and Health Care Management, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. Ingolstaedter Landstrasse 1, D85764, Neuherberg/Munich, Germany

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Particle and Fibre Toxicology 2010, 7:27  doi:10.1186/1743-8977-7-27

Published: 29 September 2010

Abstract

Rationale

Several epidemiological studies associated exposure to increased levels of particulate matter in Augsburg, Germany with cardiovascular mortality and morbidity. To elucidate the mechanisms of cardiovascular impairments we investigated the cardiopulmonary responses in spontaneously hypertensive rats (SHR), a model for human cardiovascular diseases, following intratracheal instillation of dust samples from Augsburg.

Methods

250 μg, 500 μg and 1000 μg of fine ambient particles (aerodynamic diameter <2.5 μm, PM2.5-AB) collected from an urban background site in Augsburg during September and October 2006 (PM2.5 18.2 μg/m3, 10,802 particles/cm3) were instilled in 12 months old SHRs to assess the inflammatory response in bronchoalveolar lavage fluid (BALF), blood, lung and heart tissues 1 and 3 days post instillation. Radio-telemetric analysis was performed to investigate the cardiovascular responses following instillation of particles at the highest dosage based on the inflammatory response observed.

Results

Exposure to 1000 μg of PM2.5-AB was associated with a delayed increase in delta mean blood pressure (ΔmBP) during 2nd-4th day after instillation (10.0 ± 4.0 vs. -3.9 ± 2.6 mmHg) and reduced heart rate (HR) on the 3rd day post instillation (325.1 ± 8.8 vs. 348.9 ± 12.5 bpm). BALF cell differential and inflammatory markers (osteopontin, interleukin-6, C-reactive protein, and macrophage inflammatory protein-2) from pulmonary and systemic level were significantly induced, mostly in a dose-dependent way. Protein analysis of various markers indicate that PM2.5-AB instillation results in an activation of endothelin system (endothelin1), renin-angiotensin system (angiotensin converting enzyme) and also coagulation system (tissue factor, plasminogen activator inhibitor-1) in pulmonary and cardiac tissues during the same time period when alternation in ΔmBP and HR have been detected.

Conclusions

Our data suggests that high concentrations of PM2.5-AB exposure triggers low grade PM mediated inflammatory effects in the lungs but disturbs vascular homeostasis in pulmonary tissues and on a systemic level by affecting the renin angiotensin system, the endothelin system and the coagulation cascade. These findings are indicative for promotion of endothelial dysfunction, atherosclerotic lesions, and thrombogeneis and, thus, provide plausible evidence that susceptible-predisposed individuals may develop acute cardiac events like myocardial infarction when repeatedly exposed to high pollution episodes as observed in epidemiological studies in Augsburg, Germany.