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

Publisher: BioMed Central Country of Publication: England NLM ID: 101236354 Publication Model: Electronic Cited Medium: Internet ISSN: 1743-8977 (Electronic) Linking ISSN: 17438977 NLM ISO Abbreviation: Part Fibre Toxicol Subsets: MEDLINE

Original Publication: London : BioMed Central, 2004-

Dust*; Cardiovascular Diseases/*etiology ; Inflammation/*etiology ; Particulate Matter/*toxicity; Acute-Phase Reaction ; Animals ; Blood Pressure ; C-Reactive Protein/analysis ; Germany ; Heart/drug effects ; Heart Rate ; Homeostasis ; Injections, Spinal ; Lung/chemistry ; Lung/pathology ; Male ; Myocardium/chemistry ; Myocardium/pathology ; Rats ; Rats, Inbred SHR

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 2(nd)-4(th) 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.

Comment in: Part Fibre Toxicol. 2011;8:12; author reply 12. (PMID: 21406084)

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0 (Dust)
0 (Particulate Matter)
9007-41-4 (C-Reactive Protein)

Date Created: 20101006 Date Completed: 20101203 Latest Revision: 20211020

20231215

PMC2956709

10.1186/1743-8977-7-27

20920269