Nanoparticles alter cyclooxygenase activity in microvascular dysfunction

Details

• Personal Author:
  Castranova, Vincent ; Chen B ; Cumpston J ; Frazer D ; Knuckles TL ; Nurkiewicz TR ; Yi J ; Castranova, Vincent ; Chen B ; Cumpston J ; Frazer D ; Knuckles TL ; Nurkiewicz TR ; Yi J
• Description:
  The widespread increase in the production and use of nanomaterials has increased the potential for nanoparticle exposure; however, little is known about the biologic effects of nanoparticle inhalation. We have shown that blunted nitric oxide (NO) production significantly contributes to nanoparticle induced microvascular dysfunction. However, it cannot account for all of the microvascular effects of nanoparticle exposure. The purpose of this study was to evaluate alternative mechanisms of microvascular dysfunction. Rats were exposed to nano-TiO2 (primary particle size approximately 21 nm) aerosols in our Inhalation Facility at a concentration of 4-5 mg/m3 with a count median aerodynamic diameter of approximately 145 nm for 4-6 hours yielding a total calculated lung burden of 30 microg. 24 h post-exposure, the spinotrapezius muscle was prepared for intravital microscopy. We assessed arteriolar function via perivascular nerve stimulation and active hyperemia with or without inhibitors for endogenous NO production or cyclooxygenase (COX) products. NO inhibition increased vasoconstriction and decreased vasodilation in control but not in exposed animals. COX inhibition had no effect on vasoconstriction in either group but overtly blunted vasodilation in exposed animals. Based on these results, we then determined if exposure altered sensitivity to COX products. Suffusion of the muscle with U46619 (1-100 nM), a thromboxane A2 mimetic, led to a significantly greater vasoconstriction in exposed animals compared to control (max % of control -22 +/- 3.4% sham, -31 +/- 4.0% exposed). Furthermore, suffusion of iloprost (2.8-28 nM), a prostacyclin mimetic, led to a slight increase in vasodilation in the exposed animals compared to control (max % of control 177 +/- 25% sham, 214 +/- 41% exposed). Hence, the compensatory mechanism for the NO deficit appears to be COX mediated, through enhanced sensitivity and possibly increased endogenous production. [Description provided by NIOSH]
• Subjects:
  Aerosols Air Pollutants, Occupational Cardiovascular Diseases Cardiovascular System Hazardous Substances Irritants Laboratories Lung Lung Diseases Occupational Health Particulate Matter Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Aerosol-particles Airborne-particles Biohazards Biological-effects Cardiopulmonary-system Cardiopulmonary-system-disorders Cardiovascular-disease Cardiovascular-system Cardiovascular-system-disorders Cellular-reactions Inhalation-studies Laboratory-animals Lung-disorders Lung-irritants Nanotechnology Particulates Physiological-effects Pulmonary-disorders Pulmonary-system-disorders Quantitative-analysis Respiratory-hypersensitivity Respiratory-irritants Respiratory-system-disorders Statistical-analysis Vasoactive-agents

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Abstract or Summary
• Place as Subject:
  District of Columbia ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Volume:
  120
• NIOSHTIC Number:
  nn:20038591
• Citation:
  Toxicologist 2011 Mar; 120(Suppl 2):316
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9) ; Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Construction ; Manufacturing ; Construction ; Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
• Supplement:
  2
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:dc326fe2793915a491f8decccec41d93ccc6f8458d9a20a77a0213a2a18cf3ca94e2b00cf5caa59337d9fb4365136c6e7fc147151c7aa604c941992bf300aad9
• Download URL:
  https://stacks.cdc.gov/view/cdc/192244/cdc_192244_DS1.pdf
• File Type:
  [PDF - 1.10 MB ]