Fig. 2.

Airways of GSNOR^−/− mice are hyporeactive to methacholine (MCh) and allergen challenge. Total pulmonary resistances (R_T) of WT and GSNOR^−/− (KO) mice after control (nonallergic; PBS) (A) and allergen (OVA) (B) treatment were determined in the absence or presence of various concentrations of MCh administered intravenously. R_T values in PBS-treated and in OVA-treated GSNOR^−/− mice were significantly lower than in WT controls [KO PBS versus WT PBS, P < 0.001; KO OVA versus WT OVA, P < 0.004; analysis of variance (ANOVA) and post-hoc analyses at 3- to 5-MCh doses]. Data represent the mean + SE of at least 7 to 10 mice per group. (C) The incremental effect of OVA (over PBS control) on WT and GSNOR^−/− mice [OVA minus PBS (OVA-PBS)]. Whereas R_T of WT mice increased significantly after OVA treatment (WT PBS versus WT OVA, P < 0.04; ANOVA), the R_T of GSNOR ^−/− mice did not change significantly (KO PBS versus KO OVA, P = 0.1; ANOVA). (D) Effect of the iNOS inhibitor 1400W on airway responsiveness in PBS- and OVA-treated WT mice (WT PBS versus WT PBS + 1400W, P = 0.12, n = 5 to 9; WT OVA versus WT OVA + 1400W, P = 0.22, n = 7 to 9). (E) Effect of iNOS inhibition by 1400W on airway responsiveness in GSNOR^−/− mice. Administration of 1400W to OVA-treated GSNOR^−/− mice resulted in a significant increase in airway resistance (KO OVA versus KO OVA + 1400W, P < 0.02, n = 5 to 9; ANOVA). (F) Protein S-nitrosylation (SNO) in lung homogenates of OVA-treated mice. iNOS inhibition (1400W) reduces SNO levels in GSNOR^−/− mice (*, P < 0.05, n = 3).