Abstract 5500: Nanoparticle Inhalation Impairs Endothelium-dependent Vasoreactivity in Coronary Arterioles

Autor: Amanda J LeBlanc, Yanduan Hu, Judy M Muller-Delp, B. T Chen, D. Frazer, V. Castranova, Timothy R Nurkiewicz
Rok vydání: 2008
Předmět:
Zdroj: Circulation. 118
ISSN: 1524-4539
0009-7322
DOI: 10.1161/circ.118.suppl_18.s_562
Popis: Epidemiological studies have shown that exposure to particulate matter (PM) is associated with an increased risk for myocardial infarction (MI). We have recently shown that systemic microvascular function is significantly impaired after inhalation exposure to PM and nanoparticles. However, it remains unclear how endothelial function in the coronary microcirculation responds to such insults and if impaired vasoreactivity as a result of exposure contributes to the increased risk for MI. Male Sprague-Dawley rats were exposed to filtered air (control), fine TiO 2 particles (primary particle diameter, ~1μm), or TiO 2 nanoparticles (primary particle diameter, ~21 nm) via inhalation at concentrations relevant to ambient air pollution (Fine TiO 2 , ~ 8–90 μg measured pulmonary deposition; nano-TiO 2 , ~ 4–38 μg measured pulmonary deposition). Coronary arterioles (≤ 150 μm in diameter) were isolated from the left anterior descending artery distribution and responses to flow (FID), acetylcholine (ACh), endothelin and dea-NONO-ate were assessed. Exposure to either fine TiO 2 or nano-TiO 2 impaired endothelium-dependent FID (Control 78±8%, Fine TiO 2 62±5%, Nano-TiO 2 60±8%). Similarly, endothelium-dependent vasodilation to ACh tended to be lower in coronary arterioles from rats exposed to fine TiO 2 and nano-TiO 2 compared to arterioles from control rats, but this did not reach statistical significance. Interestingly, vascular smooth muscle nitric oxide (NO) sensitivity (dea-NONO-ate) was decreased by exposure to nano-TiO 2 , but not fine TiO 2 (Nano-TiO 2 36±8%, Fine TiO 2 69±5%). Furthermore, nano-TiO 2 exposure diminished vasoconstrictor responses to endothelin, whereas fine TiO 2 exposure had no effect on endothelin reactivity (Nano-TiO 2 65±6%, Fine TiO 2 80±4%). These results suggest that nanoparticle exposure causes significantly more microvascular dysfunction than exposure to fine TiO 2 . It is probable that such disturbances in coronary microvascular function contribute to the cardiac events associated with particle pollution exposure. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.
Databáze: OpenAIRE