title: Pulmonary cerium dioxide nanoparticle exposure differentially impairs coronary and mesenteric arteriolar reactivity.
abstract: Cerium dioxide nanoparticles (CeO2 NPs) are an engineered nanomaterial (ENM) that possesses unique catalytic, oxidative, and reductive properties. Currently, CeO2 NPs are being used as a fuel catalyst but these properties are also utilized in the development of potential drug treatments for radiation and stroke protection. These uses of CeO2 NPs present a risk for human exposure; however, to date, no studies have investigated the effects of CeO2 NPs on the microcirculation following pulmonary exposure. Previous studies in our laboratory with other nanomaterials have shown impairments in normal microvascular function after pulmonary exposures. Therefore, we predicted that CeO2 NP exposure would cause microvascular dysfunction that is dependent on the tissue bed and dose. Twenty-four-hour post-exposure to CeO2 NPs (0-400 μg), mesenteric, and coronary arterioles was isolated and microvascular function was assessed. Our results provided evidence that pulmonary CeO2 NP exposure impairs endothelium-dependent and endothelium-independent arteriolar dilation in a dose-dependent manner. The CeO2 NP exposure dose which causes a 50 % impairment in arteriolar function (EC50) was calculated and ranged from 15 to 100 μg depending on the chemical agonist and microvascular bed. Microvascular assessments with acetylcholine revealed a 33-75 % reduction in function following exposure. Additionally, there was a greater sensitivity to CeO2 NP exposure in the mesenteric microvasculature due to the 40 % decrease in the calculated EC50 compared to the coronary microvasculature EC50. CeO2 NP exposure increased mean arterial pressure in some groups. Taken together, these observed microvascular changes may likely have detrimental effects on local blood flow regulation and contribute to cardiovascular dysfunction associated with particle exposure.
authors: Center for Cardiovascular and Respiratory Sciences, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, 1 Medical Center Drive, PO Box 9105, Morgantown, WV, 26506-9105, USA.
authors: Valerie C
authors: VC
authors: Minarchick
authors: Phoebe A
authors: PA
authors: Stapleton
authors: Dale W
authors: DW
authors: Porter
authors: Michael G
authors: MG
authors: Wolfarth
authors: Engin
authors: E
authors: Çiftyürek
authors: Mark
authors: M
authors: Barger
authors: Edward M
authors: EM
authors: Sabolsky
authors: Timothy R
authors: TR
authors: Nurkiewicz
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002563:Cerium / Q000633:toxicity*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D053758:Nanoparticles / Q000633:toxicity*; D009924:Organ Culture Techniques; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D002563:Cerium; C030583:ceric oxide
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