Intratracheal instillation of TiO 2 increases carotid‐femoral pulse wave velocity by suppression of eNOS and increasing IL‐6 in artery in rat

Background In addition to the damages to the lungs, inhaled nanoparticles may induce systemic proinflammatory and prothrombotic effects; however, its impacts to the alternation of arterial wall property have not been investigated. Methods Studies were performed on 32 male Sprague‐Dawley rats in 4 groups, in terms of different interventions [intratracheal instillation of titian dioxide (TiO 2 ; D=20 nm; 4 mg/kg) or vehicle] and treatments [N‐acetylcysteine (NAC; 20 mg/kg; i.v.) or Xigris (10 mg/kg; i.v.); 5 min prior to TiO 2 instillation]. The LV function and the carotid‐femoral pulse wave velocity (CFPWV) were assessed by the LV pressure‐volume and two intravascular pressure transducers, respectively. Blood were samples at baseline, 1, 3 and 5 hrs after TiO 2 to assess serum creatine phosphokinase (CPK) and creatine kinase‐MB (CK‐MB). Nitric oxide (NO), methylguanidiene (MG), malondialdehyde (MDA) and C‐reactive protein (CRP) were examined at 5 hrs. The expressions of IL‐6 and eNOS in the thoracic aorta were examined. Results TiO 2 instillation induced severe systemic thrombotic effects, increasing CFPWV by 50% (8.8±3.6 m/s vs. 13.7±4.0 m/s). Xigris pretreatment attenuated thrombotic effects with minor changes in biomarkers and CFPWV (12.9±4.1 m/s). NAC pretreatment attenuated the increase in CFPWV (10.1±2.6 m/s; P<0.05) along with reduced serum MG, MDA and CRP and tissue IL‐6 and increased eNOS, while thrombotic effects persisted. Conclusion Intratracheal instillation of TiO 2 induced transit increase in arterial stiffness is associated with systemic inflammatory responses.