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 TiO2 particles (primary particle diameter, approximately 1um), or TiO2 nanoparticles (primary particle diameter, approximately 21 nm) via inhalation at concentrations relevant to ambient air pollution (Fine TiO2, approximately 8-90 ug measured pulmonary deposition; nano-TiO2, approximately 4-38 ug measured pulmonary deposition). Coronary arterioles (< or = 150 um 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 TiO2 or nano-TiO2 impaired endothelium-dependent FID (Control 78+/-8%, Fine TiO2 62+/-5%, Nano-TiO2 60+/-8%). Similarly, endothelium-dependent vasodilation to ACh tended to be lower in coronary arterioles from rats exposed to fine TiO2 and nano-TiO2 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-TiO2, but not fine TiO2 (Nano-TiO2 36+/-8%, Fine TiO2 69+/-5%). Furthermore, nano-TiO2 exposure diminished vasoconstrictor responses to endothelin, whereas fine TiO2 exposure had no effect on endothelin reactivity (Nano-TiO2 65+/-6%, Fine TiO2 80+/-4%). These results suggest that nanoparticle exposure causes significantly more microvascular dysfunction than exposure to fine TiO2. It is probable that such disturbances in coronary microvascular function contribute to the cardiac events associated with particle pollution exposure.
Epidemiology; Particulate-dust; Cardiac-function; Cardiovascular-disease; Cardiovascular-system-disease; Myocardial-disorders; Myocardium; Inhalation-studies; Air-sampling; Airborne-dusts; Airborne-particles; Respiratory-function-tests; Respiratory-irritants; Respiratory-system-disorders; Aerosol-particles; Biological-effects; Biological-function; Biological-transport; Blood-vessels; Laboratory-animals; Nanotechnology
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, M/S 4020, Morgantown, WV 26505