Inhalation of ultrafine titanium dioxide augments particle-dependent microvascular dysfunction.
Nurkiewicz TR; Porter DW; Hubbs AF; Millecchia L; Frazer AM; Chen BT; Frazer D; Castranova V; Boegehold MA
FASEB J 2007 Apr; 21(6)(Suppl):A846
We have shown that pulmonary exposure to fine particulate matter (PM) impairs endothelium dependent dilation in systemic arterioles. Ultrafine PM has been suggested to be more toxic by virtue of its increased surface area. The purpose of this study was to determine if ultrafine PM inhalation produces greater microvascular dysfunction than fine PM. Rats were exposed to fine or ultrafine TiO2 via inhalation (mean particle diameters of approximately 1 µm, and approximately 123 nm, respectively) at concentrations relevant to ambient air pollution. The spinotrapezius muscle was prepared for in vivo microscopy 24 hours after pulmonary exposures. Intraluminal infusion of the Ca2+ ionophore A23187 was used to evaluate endothelium dependent arteriolar dilation. In control rats, A23187 infusion produced dose-dependent arteriolar dilations. In rats exposed to fine TiO2, A23187 infusion elicited vasodilations that were blunted in proportion to pulmonary particle deposition. In rats exposed to ultrafine TiO2, A23187 infusion produced arteriolar constrictions or significantly impaired vasodilator responses as compared to the responses observed in control rats or those exposed to an identical pulmonary load of fine particles. Various tissues were harvested for pathological analysis and measurements of pulmonary load and peripheral particle deposition. These observations suggest that at equivalent pulmonary loads, as compared to fine TiO2, ultrafine TiO2 inhalation produces greater remote microvascular dysfunction.
Cell-function; Mathematical-models; Statistical-analysis; Lung-function; Lung-cells; Pulmonary-function; Pulmonary-system; Biological-function; Biological-monitoring; Animal-studies; Air-flow; Particle-aerodynamics; Tissue-disorders; Inhalation-studies; In-vivo-studies; Blood-vessels; Nanotechnology
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