title: Nanoparticle inhalation augments particle-dependent systemic microvascular dysfunction.
abstract: BACKGROUND
  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 inherently more toxic by virtue of its increased surface area. The purpose of this study was to determine if ultrafine PM (or nanoparticle) inhalation produces greater microvascular dysfunction than fine PM. Rats were exposed to fine or ultrafine TiO2 aerosols (primary particle diameters of ~1 mum and ~21 nm, respectively) at concentrations which do not alter bronchoalveolar lavage markers of pulmonary inflammation or lung damage.
  
  
  RESULTS
  By histopathologic evaluation, no significant inflammatory changes were seen in the lung. However, particle-containing macrophages were frequently seen in intimate contact with the alveolar wall. The spinotrapezius muscle was prepared for in vivo microscopy 24 hours after inhalation 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 a similar pulmonary load of fine particles.
  
  
  CONCLUSIONS
  These observations suggest that at equivalent pulmonary loads, as compared to fine TiO2, ultrafine TiO2 inhalation produces greater remote microvascular dysfunction.
authors.affiliation: Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, Morgantown, WV, USA. tnurkiewicz@hsc.wvu.edu.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Nurkiewicz
authors.forename: Dale W
authors.initials: DW
authors.lastname: Porter
authors.forename: Ann F
authors.initials: AF
authors.lastname: Hubbs
authors.forename: Jared L
authors.initials: JL
authors.lastname: Cumpston
authors.forename: Bean T
authors.initials: BT
authors.lastname: Chen
authors.forename: David G
authors.initials: DG
authors.lastname: Frazer
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova