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• Stapleton, PA.
• Minarchick, VC.
• Cumpston, AM.
• McKinney, W
• Chen, BT.
• Sager, TM.
• Frazer, DG.
• Mercer, RR.
• Scabilloni, J
• Andrew, ME.
• Castranova, V
• Nurkiewicz, TR.
• [+] on Google Scholar
• Stapleton, PA.
• Minarchick, VC.
• Cumpston, AM.
• McKinney, W
• Chen, BT.
• Sager, TM.
• Frazer, DG.
• Mercer, RR.
• Scabilloni, J
• Andrew, ME.
• Castranova, V
• Nurkiewicz, TR.
• [+] on PubMed
• Stapleton, PA.
• Minarchick, VC.
• Cumpston, AM.
• McKinney, W
• Chen, BT.
• Sager, TM.
• Frazer, DG.
• Mercer, RR.
• Scabilloni, J
• Andrew, ME.
• Castranova, V
• Nurkiewicz, TR.

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Int. J. Mol. Sci. 2012, 13(11), 13781-13803; doi:10.3390/ijms131113781

Article

Impairment of Coronary Arteriolar Endothelium-Dependent Dilation after Multi-Walled Carbon Nanotube Inhalation: A Time-Course Study

Phoebe A. Stapleton ^1,2 , Valerie C. Minarchick ^1,2 , Amy M. Cumpston ³ , Walter McKinney ³ , Bean T. Chen ³ , Tina M. Sager ³ , David G. Frazer ^2,3 , Robert R. Mercer ³ , James Scabilloni ³ , Michael E. Andrew ⁴ , Vincent Castranova ³  and Timothy R. Nurkiewicz ^1,2,3,5,*

¹ Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, WV 26506, USA ² Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV 26506, USA ³ Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA ⁴ Biostatistics and Epidemiology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA ⁵ Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, WV 26505, USA

* Author to whom correspondence should be addressed.

Received: 17 September 2012; in revised form: 12 October 2012 / Accepted: 16 October 2012 / Published: 24 October 2012

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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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.

Keywords: microcirculation; coronary; arteriole; nanotoxicology; multi-walled carbon nanotube; engineered nanomaterial; translocation

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