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Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways.

Authors
Knuckles-TL; Yi-J; Frazer-DG; Leonard-HD; Chen-BT; Castranova-V; Nurkiewicz-TR
Source
Nanotoxicology 2012 Nov; 6(7):724-735
NIOSHTIC No.
20039348
Abstract
The widespread increase in the production and use of nanomaterials has increased the potential for nanoparticle exposure; however, the biological effects of nanoparticle inhalation are poorly understood. Rats were exposed to nanosized titanium dioxide aerosols (10 mg lung burden); at 24 h post-exposure, the spinotrapezius muscle was prepared for intravital microscopy. Nanoparticle exposure did not alter perivascular nerve stimulation (PVNS)-induced arteriolar constriction under normal conditions; however, adrenergic receptor inhibition revealed a more robust effect. Nanoparticle inhalation reduced arteriolar dilation in response to active hyperaemia (AH). In both PVNS and AH experiments, nitric oxide synthase (NOS) inhibition affected only controls. Whereas cyclooxygenase (COX) inhibition only attenuated AH-induced arteriolar dilation in nanoparticle-exposed animals. This group displayed an enhanced U46619 constriction and attenuated iloprost-induced dilation. Collectively, these studies indicate that nanoparticle exposure reduces microvascular NO bioavailability and alters COX-mediated vasoreactivity. Furthermore, the enhanced adrenergic receptor sensitivity suggests an augmented sympathetic responsiveness.
Keywords
Aerosol-particles; Airborne-particles; Biological-effects; Exposure-assessment; Inhalants; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung-function; Microscopic-analysis; Nanotechnology; Physical-properties; Physiological-effects; Physiological-measurements; Physiological-response; Pulmonary-function; Pulmonary-system; Quantitative-analysis; Respiratory-hypersensitivity; Vasoactive-agents; Author Keywords: Microvascular; sympathetic nervous system; wholebody inhalation; nitric oxide; titanium dioxide
Contact
Timothy R. Nurkiewicz, Department of Physiology & Pharmacology, Center for Cardiovascular and Respiratory Sciences, Robert C. Byrd Health Sciences Center, 1 Medical Center Drive, West Virginia University, Morgantown, WV 26506
CAS No.
13463-67-7; 10102-43-9
Publication Date
20121101
Document Type
Journal Article
Email Address
tnurkiewicz@hsc.wvu.edu
Fiscal Year
2013
NTIS Accession No.
NTIS Price
Issue of Publication
7
ISSN
1743-5390
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Nanotoxicology
State
WV
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