title: Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways.
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 μg 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.
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, WV, USA.
authors.forename: Travis L
authors.initials: TL
authors.lastname: Knuckles
authors.forename: Jinghai
authors.initials: J
authors.lastname: Yi
authors.forename: David G
authors.initials: DG
authors.lastname: Frazer
authors.forename: Howard D
authors.initials: HD
authors.lastname: Leonard
authors.forename: Bean T
authors.initials: BT
authors.lastname: Chen
authors.forename: Vince
authors.initials: V
authors.lastname: Castranova
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Nurkiewicz
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000280:Administration, Inhalation; D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006940:Hyperemia / Q000503:physiopathology; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000633:toxicity*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000633:toxicity; D010316:Particle Size; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D016861:Cyclooxygenase Inhibitors; D011942:Receptors, Adrenergic, alpha; C009495:titanium dioxide; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D014025:Titanium; D011451:Prostaglandin-Endoperoxide Synthases