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.

Keywords::

• Microvascular
• sympathetic nervous system
• whole-body inhalation
• nitric oxide
• titanium dioxide

Acknowledgements

The authors would like to thank Carroll McBride and Kimberly Wix for their expert technical assistance in this study. We also thank Phoebe Stapleton, Ph.D., for her critical review of the manuscript. The authors would also like to thank Michael McCawley, Ph.D., for his expert technical assistance with modelling the particle distributions. Funding sources: RO-1 ES015022 and RC-1 ES018274 (TRN). Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the view of the National Institute for Occupational Safety and Health.