Ultrafine particulate matter inhalation attenuates microvascular endothelial nitric oxide production.
Nurkiewicz-TR; Porter-DW; Hubbs-AF; Chen-BT; Frazer-DG; Castranova-V
Toxicologist 2008 Mar; 102(1):258
We have shown that pulmonary exposure to fine particulate matter (PM) impairs endothelium-dependent dilation in systemic arterioles. The purposes of this study were to: determine if PM size affects the severity of microvascular dysfunction, characterize alterations in endogenous nitric oxide (NO) production, and identify systemic mechanisms that may influence NO production after PM inhalation. Rats were exposed to fine or ultrafine TiO2 via inhalation (primary particle sizes of approximately 1 mu m, and approximately 21 nm, respectively) at depositions of 10-100 mu g/rat. The spinotrapezius muscle was prepared for intravital microscopy 24 hrs after exposures. Intraluminal infusion of the Ca2+ ionophore A23187 was used to evaluate endothelium-dependent arteriolar dilation. Microvascular NO production was measured with a Clarke- Type electrochemical NO sensor. In control rats, A23187 infusion produced dosedependent 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 those observed in rats exposed to an identical pulmonary load of fine particles. Endogenous microvascular NO production was attenuated after ultrafine TiO2 inhalation in a dose-dependent manner. Treatment with either 4-aminobenzoic hydrazide or apocynin partially restored NO production and normal microvascular function. These results are consistent with the hypothesis that systemic inflammatory mechanisms are active after PM exposure and such mechanisms disturb normal microvascular function.
Particle-aerodynamics; Particulate-dust; Particulates; Inhalation-studies; Laboratory-animals; Laboratory-testing; Respiratory-function-tests; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-disorders; Pulmonary-function; Pulmonary-system-disorders; Blood-vessels; Nanotechnology
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington