title: Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment.
abstract: With the tremendous number and diverse applications of engineered nanomaterials incorporated in daily human activity, exposure can no longer be solely confined to occupational exposures of healthy male models. Cardiovascular and endothelial cell dysfunction have been established using in vitro and in situ preparations, but the translation to intact in vivo models is limited. Intravital microscopy has been used extensively to understand microvascular physiology while maintaining in vivo neurogenic, humoral, and myogenic control. However, a tissue specific model to assess the influences of nanomaterial exposure on female reproductive health has not been fully elucidated. Female Sprague Dawley (SD) rats were exposed to nano-TiO2 aerosols (171 ± 6 nm, 10.1 ± 0.39 mg/m(3), 5h) 24-hours prior to experimentation, leading to a calculated deposition of 42.0 ± 1.65 μg. After verifying estrus status, vital signs were monitored and the right horn of the uterus was exteriorized, gently secured over an optical pedestal, and enclosed in a warmed tissue bath using intravital microscopy techniques. After equilibration, significantly higher leukocyte-endothelium interactions were recorded in the exposed group. Arteriolar responsiveness was assessed using ionophoretically applied agents: muscarinic agonist acetylcholine (0.025 M; ACh; 20, 40, 100, and 200 nA), and nitric oxide donor sodium nitroprusside (0.05 M; SNP; 20, 40, and 100 nA), or adrenergic agonist phenylephrine (0.05 M; PE; 20, 40, and 100 nA) using glass micropipettes. Passive diameter was established by tissue superfusion with 10(-4)M adenosine. Similar to male counterparts, female SD rats present systemic microvascular dysfunction; however the ramifications associated with female health and reproduction have yet to be elucidated.
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, WV 26506, United States; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV 26506, United States.
authors.forename: P A
authors.initials: PA
authors.lastname: Stapleton
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, WV 26506, United States; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV 26506, United States.
authors.forename: C R
authors.initials: CR
authors.lastname: McBride
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, WV 26506, United States; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV 26506, United States.
authors.forename: J
authors.initials: J
authors.lastname: Yi
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, WV 26506, United States; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV 26506, United States. Electronic address: tnurkiewicz@hsc.wvu.edu.
authors.forename: T R
authors.initials: TR
authors.lastname: Nurkiewicz
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D049329:Nanostructures / Q000633:toxicity*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium / Q000633:toxicity*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: C009495:titanium dioxide; D009599:Nitroprusside; D010656:Phenylephrine; D014025:Titanium
keywords: Basal uterine arterioles; In vivo; Intravital microscopy; Nanotoxicology; Uterus