Effect of dietary nitrite and nitrated fatty acids on airway hyperresponsiveness and inflammation in a mouse model of asthma

Dietary nitrite (DN) generates NO that lowers blood pressure in vivo . Nitrated fatty acids (NO 2 -FAs) are formed endogenously from NO and nitrite and display broad anti-inflammatory effects including protection in an in vivo model of inflammatory bowel disease. Our aim was to investigate if DN or NO 2 -FAs affect airway hyperresponsiveness and inflammation in a mouse model of asthma. Female BALB/c mice were sensitized with OVA+Al(OH) 3 on day 0 and 7 and challenged with OVA or PBS i.n. on day 14-16. DN was administered day 10-17 by nitrite-enriched drinking water. NO 2 -FAs (5 mg/kg/day) were administrated day 10-17 by a s.c. placed osmotic pump. Airway resistance (R N ) to metacholine and inflammatory cells in bronchoalveolar lavage (BAL) were determined on day 17. OVA induced an increase in R N compare to ctrl in all groups (OVA vs. PBS; 5.3±0.2 vs. 2.3±0.1, OVA-DN vs. PBS; 5.6±0.2 vs. 2.5±0.1, OVA-NO 2 -FAs vs. PBS; 5.4±0.2 vs. 2.2±0.1 (cmH 2 0/mL), all p<0.001). No differences in R N were observed between the OVA groups with or without administration of DN or NO 2 -FAs (p>0.05). OVA induced an increase in BAL eosinophils (EOS) compared to ctrl in all groups (OVA vs. PBS; 25±5.5 vs. 0±0, OVA-DN vs. PBS; 21±4 vs. 0±0, OVA-NO 2 -FAs vs. PBS; 45±7 vs. 0.1±0 (10,000 cells/mL), all p<0.001). No difference in EOS were observed between OVA with or without administration of DN or NO 2 -FAs (p>0.05). The number of EOS were higher in OVA- NO 2 -FAs treated animals versus OVA alone (p<0.001). To conclude, neither DN nor NO 2 -FAs displayed anti-inflammatory effects in this asthma model, indicating that there is tissue specificity in the actions of these reactive nitrogen oxide species.