PMC

West Virginia University inhalation exposure facility schematic for the generation of nano-TiO₂ aerosols.

Real-time nano-TiO₂ concentrations over the exposure period. Dots represent 2-min averages with an average particle concentration of 5.7 mg/m³.

Nanoparticle inhalation exposure resulted in persistent blunting of arteriolar dilation without the influence of sympathetic nerves. α-Adrenergic blockade failed to alter the blunting of arteriolar dilation following active hyperaemia at 12 Hz in nano-TiO₂-exposed animals. Values are means ± SE. *p < 0.05 vs. control exposure.

Pulmonary nanoparticle exposure alters arteriolar responsiveness to thromboxane A₂ (TxA₂) and prostacyclin mimetics. (A) Superfusion of the spinotrapezius muscle with U46619, a TxA₂ mimetic, significantly enhanced arteriolar constriction following nano-TiO₂ exposure compared with control animals at 1 nM (n = 16 control, 13 nano-TiO₂-exposed arterioles). (B) Iloprost superfusion led to a dose-dependent arteriolar dilation that was significantly blunted at 2.8 nM following nano-TiO₂ exposure (2.8 nM n = 9 control and n = 13 nano-TiO₂ exposed; 28 nM n = 11 control and n = 16 nano-TiO₂-exposed arterioles). Values are means ± SE. *p < 0.05 vs. control exposure, ^‡p < 0.05 vs. 2.8 nM iloprost.

Nanoparticle inhalation attenuates functional arteriolar dilation during active hyperaemia. (A) Nano-TiO₂ exposure reduces arteriolar vasodilation to metabolic stimuli (n = 23 control, 31 nano-TiO₂-exposed arterioles). (B) Inhibition of NO production with N^G-monomethyl-l-arginine (L-NMMA) attenuates arteriolar dilation in control animals but not nano-TiO₂ exposed (n = eight control, nine nano-TiO₂-exposed arterioles). (C) Conversely, inhibition of cyclooxygenase impairs arteriolar dilation in nano-TiO₂-exposed animals compared with control (n = 9 control, 15 nano-TiO₂-exposed arterioles). MEC, meclofenamate. Values are means ± SE. *p < 0.05 vs. control, ^†p < 0.05 vs. control normal superfusate at the same frequency, ^‡p < 0.05 vs. nano-TiO₂-exposed normal superfusate at the same frequency.

Nanoparticle inhalation alters arteriolar responsiveness to sympathetic stimulation following L-NMMA and phentolamine treatment. PVNS was performed as described in the Methods. (A) Nano-TiO₂ exposure did not alter responsiveness to sympathetic arteriole constriction during normal PSS superfusion (n = 23 control, 27 nano-TiO₂-exposed arterioles). (B) Treatment with L-NMMA increased arteriolar constriction in control animals but not nano-TiO₂-exposed animals (n = 10 control, 12 nano-TiO₂-exposed arterioles). (C) Nano-TiO₂ exposure increased sensitivity to α-adrenergic blockade during sympathetic arteriolar constriction (n = 10 control, 11 nano-TiO₂-exposed arterioles). (D) Tetrodotoxin significantly ablated arteriolar constriction in all groups (n = four control, nine nano-TiO₂-exposed arterioles). Values are means ± SE. *p < 0.05 vs. control at same stimulation frequency, ^†p < 0.05 vs. normal superfusate at the same frequency.

Nano-TiO₂ particle size distribution. (A) Representative ELPI size distribution of the nano-TiO₂ aerosol for the 13 impactor stages (between 7 and 10,000 nm). Average nano-TiO₂ aerosol count median aerodynamic diameter (D_ae) was 161 nm. (B) Gaussian distribution of particle size based on frequency. The dotted line is the model fit for a lognormal distribution function with a median (or geometric mean) of 160 nm and a geometric standard deviation of 2.2. The lighter grey line is the actual data from the ELPI. (C) Representative SMPS size distribution curve for the nano-TiO₂ aerosol over the 107 size cut-offs (between 14 and 670 nm). Average nano-TiO₂ aerosol count geometric mean diameter (D_p) was 159 nm. (D) The dotted line is the model fit for a lognormal distribution function with a median (or geometric mean) of 160 nm and a geometric standard deviation of 2.2. The solid lighter grey line is the actual data from the SMPS.