Nanoparticle Inhalation Impairs Endothelium-Dependent Vasodilation in Subepicardial Arterioles

Abstract

Exposure to fine particulate matter (PM, mean aerodynamic diameter ≤2.5 μm) has been shown to be a risk factor for cardiovascular disease mortality and may contribute to acute coronary events such as myocardial infarction (MI). There is sufficient reason to believe that smaller particles, such as nanoparticles, might be even more detrimental than larger sized particles due to their increased surface area and higher pulmonary deposition. Our laboratory showed that nanoparticle inhalation impairs endothelium-dependent arteriolar vasodilation in skeletal muscle. However, it is not known whether coronary microvascular endothelial function is affected in a similar manner. Rats were exposed to filtered air (control) or TiO₂ nanoparticles (primary particle diameter, ∼21 nm) via inhalation at concentrations that produced measured depositions (10 μg) relevant to ambient air pollution. Subepicardial arterioles (∼150 μm in diameter) were isolated and responses to transmural pressure, flow-induced dilation (FID), acetylcholine (ACh), the Ca²⁺ ionophore A23187, and sodium nitroprusside (SNP) were assessed. Myogenic responsiveness was preserved between groups. In addition, there was no difference in the vasodilation to SNP, signifying that smooth muscle sensitivity to nitric oxide (NO) is unaffected by nano-TiO₂ exposure. However, inhalation of nano-TiO₂ produced an increase in spontaneous tone in coronary arterioles and also impaired endothelium-dependent FID. In addition, ACh-induced and A23187-induced vasodilation was also blunted in arterioles after inhalation of nano-TiO₂. Data showed that nanoparticle exposure significantly impairs endothelium-dependent vasodilation in subepicardial arterioles. Such disturbances in coronary microvascular function are consistent with the cardiac events associated with particle pollution exposure.

Acknowledgements

This work was supported by National Institutes of Health/National Institute for Environmental Health Sciences (grant R01-ES015022 to T. R. N); and Health Effects Institute Award number 4730 (T. R. N). The authors thank Carroll McBride and Kimberly Wix for their expert technical assistance in this study, and Travis Knuckles, PhD, for his help in reviewing this article. 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. Research described in this article was conducted under contract to the Health Effects Institute (HEI), an organization jointly funded by the U.S. Environmental Protection Agency (EPA) (Assistance Award R-82811201) and certain motor vehicle and engine manufacturers. The contents of this article do not necessarily reflect the views of HEI, or its sponsors, nor do they necessarily reflect the views and policies of the U.S. EPA or motor vehicle and engine manufacturers.