Pulmonary Nanoparticle Exposure Disrupts Systemic Microvascular Nitric Oxide Signaling

Details

• Personal Author:
  Boegehold MA ; Castranova, Vincent ; Chen BT ; Frazer DG ; Hubbs, Ann F. ; Nurkiewicz TR ; Porter W ; Stone S
• Description:
  We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs is/are unclear. The purpose of this study was to identify alterations in the production of reactive species and endogenous nitric oxide (NO) after nanoparticle exposure, and determine the relative contribution of hemoproteins and oxidative enzymes in this process. Sprague-Dawley rats were exposed to fine TiO2 (primary particle diameter similar to 1 mu m) and TiO2 nanoparticles (primary particle diameter similar to 21 nm) via aerosol inhalation at depositions of 4-90 mu g per rat. As in previous intravital experiments in the spinotrapezius muscle, dose-dependent arteriolar dilations were produced by intraluminal infusions of the calcium ionophore A23187. Nanoparticle exposure robustly attenuated these endothelium-dependent responses. However, this attenuation was not due to altered microvascular smooth muscle NO sensitivity because nanoparticle exposure did not alter arteriolar dilations in response to local sodium nitroprusside iontophoresis. Nanoparticle exposure significantly increased microvascular oxidative stress by similar to 60%, and also elevated nitrosative stress fourfold. These reactive stresses coincided with a decreased NO production in a particle deposition dose-dependent manner. Radical scavenging, or inhibition of either myeloperoxidase or nicotinamide adenine dinucleotide phosphate oxidase (reduced) oxidase partially restored NO production as well as normal microvascular function. These results indicate that in conjunction with microvascular dysfunction, nanoparticle exposure also decreases NO bioavailability through at least two functionally distinct mechanisms that may mutually increase local reactive species. [Description provided by NIOSH]
• Subjects:
  Animals Biochemistry Blood Chemistry Environmental Monitoring Hypersensitivity Irritants Laboratories Lung Microbiology Occupational Health Particulate Matter Respiratory Hypersensitivity Respiratory System Safety

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• Keywords:
  Animal-studies Arteriole Author Keywords: Systemic Microcirculation Biochemical-analysis Biological-effects Biological-monitoring Biological-systems Biological-transport Blood-vessels Chemical-analysis Chemical-hypersensitivity Chemical-properties Chemical-reactions Chemical-structure Chemical-synthesis Dose-response Endothelium Exposure-assessment Exposure-levels Exposure-limits Exposure-methods Inhalation Inhalation-studies Laboratory-animals Laboratory-testing Microchemistry Microscopic-analysis Microscopy Nanoparticle Nanotechnology Nitric Oxide Oxidative-processes Particle-aerodynamics Particulate-sampling-methods Particulates Pulmonary-system Respiratory-hypersensitivity Respiratory-irritants

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  191-203
• Volume:
  110
• Issue:
  1
• NIOSHTIC Number:
  nn:20035560
• Citation:
  Toxicol Sci 2009 Jul; 110(1):191-203
• Contact Point Address:
  Timothy R. Nurkiewicz, Center for Cardiovascular and Respiratory Sciences, 1 Medical Center Drive, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506-9105
• Email:
  tnurkiewicz@hsc.wvu.edu
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2009
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9416ac5f32560ec341311191c5b949f2cd58145ed74865b32433f52d1059e6c7ef9dc45968ede152c206a5592a42c0ee5481687c048227e42031cb848ff22e5c
• Download URL:
  https://stacks.cdc.gov/view/cdc/187384/cdc_187384_DS1.pdf
• File Type:
  [PDF - 550.13 KB ]