Nanoparticle inhalation modulates arteriolar sympathetic constriction: role of nitric oxide, prostanoids, and alpha-adrenergic receptors.
The widespread increase in the production and use of nanomaterials has increased the potential for nanoparticle exposure; however, little is known about the biologic effects of nanoparticle inhalation. We have previously demonstrated that inhalation of a manufactured nanomaterial, titanium dioxide (TiO2), induces systemic microvascular dysfunction. The purpose of this study was to determine if nanoparticle inhalation alters arteriolar sympathetic responsiveness. Rats were exposed to TiO2 via inhalation for a total lung burden of 10 microg. Twenty four hours following exposure, the spinotrapezius muscle was prepared for intravital microscopy and sympathetic nerve stimulation (2, 4, 8, and 16 Hz) was performed. Arteriolar constriction during stimulation was equivalent in the control and TiO2 exposed groups (max constriction -14.3±2.3 microm control,-13.7±2.5 microm TiO2). However, the addition of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor (100 microM), greatly increased the arteriolar constriction in controls (8 and 16 Hz) but not in TiO2 exposed rats (max % change -57.1±4.8 control, -39.1±4.4 TiO2). The addition of meclofenamate, a cyclooxygenase inhibitor (30 microM), had no effect on sympathetic arteriolar constriction in either group when compared to normal superfusate (max % change -42.0±4.1 control, -29.8±3.9 TiO2). Phentolamine, an alpha-adrenergic antagonist (1 microM), reduced sympathetic constriction in controls, but abolished this response in TiO2 exposed rats (max % change -22.3±3.1 control, -9.7±2.9 TiO2). These data are consistent with previous findings that indicate TiO2 exposure reduces microvascular NO bioavailability, though the compensatory mechanism remains unclear. The enhanced sensitivity to alpha-adrenergic receptor blockade following TiO2 exposure suggests an augmented responsiveness to tonic sympathetic activity.
Airborne-particles; Biological-effects; Cell-biology; Cellular-reactions; Chemical-reactions; Cytotoxic-effects; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalants; Inhalation-studies; Laboratory-animals; Laboratory-testing; Microbiology; Microscopic-analysis; Nerves; Neurological-reactions; Particle-aerodynamics; Particulate-dust; Particulates; Toxins; Vasoactive-agents
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah