title: Impairment of coronary arteriolar endothelium-dependent dilation after multi-walled carbon nanotube inhalation:  a time-course study.
abstract: Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24-168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and α-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed.
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, WV 26506, USA. tnurkiewicz@hsc.wvu.edu
authors.forename: Phoebe A
authors.initials: PA
authors.lastname: Stapleton
authors.forename: Valerie C
authors.initials: VC
authors.lastname: Minarchick
authors.forename: Amy M
authors.initials: AM
authors.lastname: Cumpston
authors.forename: Walter
authors.initials: W
authors.lastname: McKinney
authors.forename: Bean T
authors.initials: BT
authors.lastname: Chen
authors.forename: Tina M
authors.initials: TM
authors.lastname: Sager
authors.forename: David G
authors.initials: DG
authors.lastname: Frazer
authors.forename: Robert R
authors.initials: RR
authors.lastname: Mercer
authors.forename: James
authors.initials: J
authors.lastname: Scabilloni
authors.forename: Michael E
authors.initials: ME
authors.lastname: Andrew
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Nurkiewicz
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004108:Dilatation, Pathologic; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D037742:Nanotubes, Carbon / Q000633:toxicity*; D009599:Nitroprusside / Q000494:pharmacology; D009929:Organ Size; D010656:Phenylephrine / Q000494:pharmacology; D011014:Pneumonia / Q000209:etiology / Q000473:pathology; D051381:Rats; D013997:Time Factors
chemical_list: D037742:Nanotubes, Carbon; D009599:Nitroprusside; D010656:Phenylephrine; D000109:Acetylcholine