title: Nanoparticle inhalation impairs coronary microvascular reactivity via a local reactive oxygen species-dependent mechanism.
abstract: 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 TiO(2) nanoparticles via inhalation to produce a pulmonary deposition of 10 microg. 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-TiO(2) 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-TiO(2). Arachidonic acid induced vasoconstriction in coronary arterioles from rats exposed to nano-TiO(2), 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.
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, 26506-9105, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: LeBlanc
authors.forename: A M
authors.initials: AM
authors.lastname: Moseley
authors.forename: B T
authors.initials: BT
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Frazer
authors.forename: V
authors.initials: V
authors.lastname: Castranova
authors.forename: T R
authors.initials: TR
authors.lastname: Nurkiewicz
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects; D001835:Body Weight / Q000502:physiology; D002196:Capillaries / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D009569:Nitric Oxide / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011453:Prostaglandins / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013931:Thromboxanes / Q000494:pharmacology; D014025:Titanium / Q000633:toxicity; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D011453:Prostaglandins; D017382:Reactive Oxygen Species; D013931:Thromboxanes; C009495:titanium dioxide; D016718:Arachidonic Acid; D009569:Nitric Oxide; D014025:Titanium