Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways.
Knuckles TL; Yi-J; Frazer DG; Leonard HD; Chen BT; Castranova V; Nurkiewicz TR
Nanotoxicology 2012 Nov; 6(7):724-735
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 mg 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.
Aerosol-particles; Airborne-particles; Biological-effects; Exposure-assessment; Inhalants; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung-function; Microscopic-analysis; Nanotechnology; Physical-properties; Physiological-effects; Physiological-measurements; Physiological-response; Pulmonary-function; Pulmonary-system; Quantitative-analysis; Respiratory-hypersensitivity; Vasoactive-agents;
Author Keywords: Microvascular; sympathetic nervous system; wholebody inhalation; nitric oxide; titanium dioxide
Timothy R. Nurkiewicz, Department of Physiology & Pharmacology, Center for Cardiovascular and Respiratory Sciences, Robert C. Byrd Health Sciences Center, 1 Medical Center Drive, West Virginia University, Morgantown, WV 26506