Nanoparticle Inhalation Impairs Coronary Microvascular Reactivity via a Local Reactive Oxygen Species-Dependent Mechanism

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• Personal Author:
  Castranova, Vincent ; Chen BT ; Frazer D ; LeBlanc AJ ; Moseley AM ; Nurkiewicz TR
• Description:
  We have shown that nanoparticle inhalation impairs endothelium-dependent vasodilation in coronary arterioles. It is unknown whether local reactive oxygen species (ROS) contribute to this effect. Rats were exposed to TiO2 nanoparticles via inhalation to produce a pulmonary deposition of 10 mu g. Coronary arterioles were isolated from the left anterior descending artery distribution, and responses to acetylcholine, arachidonic acid, and U46619 were assessed. Contributions of nitric oxide synthase and prostaglandin were assessed via competitive inhibition with N-G-Monomethyl-L-Arginine (L-NMMA) and indomethacin. Microvascular wall ROS were quantified via dihydroethidium (DHE) fluorescence. Coronary arterioles from rats exposed to nano-TiO2 exhibited an attenuated vasodilator response to ACh, and this coincided with a 45% increase in DHE fluorescence. Coincubation with 2,2,6,6-tetramethylpiperidine-N-oxyl and catalase ameliorated impairments in ACh-induced vasodilation from nanoparticle exposed rats. Incubation with either L-NMMA or indomethacin significantly attenuated ACh-induced vasodilation in sham-control rats, but had no effect in rats exposed to nano-TiO2. Arachidonic acid induced vasoconstriction in coronary arterioles from rats exposed to nano-TiO2, but dilated arterioles from sham-control rats. These results suggest that nanoparticle exposure significantly impairs endothelium-dependent vasoreactivity in coronary arterioles, and this may be due in large part to increases in microvascular ROS. Furthermore, altered prostanoid formation may also contribute to this dysfunction. Such disturbances in coronary microvascular function may contribute to the cardiac events associated with exposure to particles in this size range. [Description provided by NIOSH]
• Subjects:
  Cardiovascular Diseases Cardiovascular System Environmental Monitoring Hazardous Substances Laboratories Lung Lung Diseases Microbiology Occupational Health Particulate Matter Respiratory System Risk Assessment Risk Factors Safety Titanium

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• Keywords:
  Arteriole Author Keywords: Microcirculation Biological-effects Cardiopulmonary-function Cardiopulmonary-system Cardiovascular-function Cardiovascular-system Cardiovascular-system-disorders Coronary Exposure-assessment Exposure-levels Exposure-methods Inhalation Inhalation-studies Laboratory-animals Laboratory-testing Lung-disorders Lung-function Microscopic-analysis Nanoparticle Nanotechnology Particulate-dust Particulates Physiological-effects Pulmonary-system Reactive Oxygen Species Risk-factors Titanium Dioxide Toxic-effects Vasoactive-agents Vasodilation

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• ISSN:
  1530-7905
• 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:
  27-36
• Volume:
  10
• Issue:
  1
• NIOSHTIC Number:
  nn:20036496
• Citation:
  Cardiovasc Toxicol 2010 Mar; 10(1):27-36
• Contact Point Address:
  TR Nurkiewicz, Center for Cardiovascular and Respiratory Sciences, 1 Medical Center Drive, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, Morgantown, WV 26506-9105
• Email:
  tnurkiewicz@hsc.wvu.edu
• Federal Fiscal Year:
  2010
• Peer Reviewed:
  True
• Source Full Name:
  Cardiovascular Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:eb2ef2986566cb4ea0f5ef13a94b2703baf82b6d517e0c69839e279852bcce03e50d504a7e1e0bec5cf5f431567cb9c06b39556bcf2c5744cc33456d21613b3b
• Download URL:
  https://stacks.cdc.gov/view/cdc/187897/cdc_187897_DS1.pdf
• File Type:
  [PDF - 558.81 KB ]