Calcium-dependent vasodilation is impaired in coronary arterioles after nanoparticle inhalation.
LeBlanc-AJ; Cumpston-J; Chen-B; Frazer-D; Castranova-V; Nurkiewicz-T
Toxicologist 2009 Mar; 108(1):278
Epidemiological studies have shown that exposure to particle pollution is associated with an increased risk for myocardial infarction (MI). This laboratory has shown in skeletal muscle that nanoparticle exposure produces significantly greater microvascular dysfunction than larger particles of the same composition. However, it remains unclear if coronary microvascular endothelial function is affected to a similar degree. Rats were exposed to filtered air (control) or TiO2 nanoparticles (primary particle diameter, ~21 nm) via inhalation at concentrations relevant to ambient air pollution (9.5 mu g measured pulmonary deposition). Coronary arterioles (~150 mu m in diameter) were isolated from the left anterior descending artery distribution and responses to flow (FID) (5-25 uL/min), acetylcholine (ACh, 10(-7) - 10(-5) M), and the Ca(2+) ionophore, A23187 (10(-8) - 10(-6) M), were assessed. Endothelium-dependent FID was preserved in coronary arterioles from rats exposed to nano-TiO2 compared to control rats. Conversely, a profound vasoconstriction (16+/-14, % constriction) resulted from cumulative additions of ACh in arterioles from rats exposed to nanoparticles, whereas control rats responded by vasodilation (73+/-4, % dilation). Similarly, nanoparticle exposure impaired arteriolar dilation to A23187 as compared to control rats. Sodium nitroprusside (10(-3) M) produced comparable arteriolar dilation in both groups, indicating that vascular smooth muscle NO responsiveness remains intact after nanoparticle exposure. These results suggest that nanoparticle exposure significantly impairs Ca(2+)-dependent microvascular responses to ACh and A23187, whereas responsiveness to shear stress is preserved. It is probable that such disturbances in coronary microvascular function contribute to the cardiac events associated with particle pollution exposure.
Biological-effects; Biological-factors; Cardiovascular-function; Cardiovascular-system; Cardiovascular-system-disorders; Epidemiology; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalation-studies; Laboratory-animals; Musculoskeletal-system; Musculoskeletal-system-disorders; Microscopic-analysis; Particle-aerodynamics; Particulate-dust; Particulates; Pollutants; Pollution; Statistical-analysis; Skeletal-disorders; Skeletal-system-disorders; Nanotechnology
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland