Ultrafine Particulate Matter Inhalation Attenuates Microvascular Endothelial Nitric Oxide Production

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• Personal Author:
  Castranova, Vincent ; Chen BT ; Frazer DG ; Hubbs, Ann F. ; Nurkiewicz TR ; Porter DW
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Blood Irritants Laboratories Lung Lung Diseases Occupational Health Particulate Matter Respiratory Function Tests Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Blood-vessels Inhalation-studies Laboratory-animals Laboratory-testing Nanotechnology Particle-aerodynamics Particulate-dust Particulates Pulmonary-disorders Pulmonary-function Pulmonary-system-disorders Respiratory-function-tests Respiratory-hypersensitivity Respiratory-irritants Respiratory-system-disorders

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 10 ; OSHA Region 3 ; Washington ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  102
• Issue:
  1
• NIOSHTIC Number:
  nn:20033603
• Citation:
  Toxicologist 2008 Mar; 102(1):258
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2008
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f5a177a14e70ce0857f712c5ab07444a4f6c26ade1feb285e8560de0dde39b04ba581862c045ca9e347ebb38c31cb8d13c08dfd674138440aa647e68873ddab0
• Download URL:
  https://stacks.cdc.gov/view/cdc/189102/cdc_189102_DS1.pdf
• File Type:
  [PDF - 7.81 MB ]