Effect of Inhibition of Nitric Oxide Synthase on Pseudomonas aeruginosa Infection of Respiratory Mucosa In Vitro

We studied the effect of the nitric oxide synthase (NOS) inhibitor asymmetric dimethyl arginine (ADMA) and the inactive enantiomer N G-methyl-d-arginine (d-NMMA) on Pseudomonas aeruginosa infection of the respiratory mucosa in nasal turbinate organ cultures. We also investigated the effect of P. aeruginosa culture filtrate on the expression of inducible NOS (iNOS) messenger RNA (mRNA) by an epithelial cell line (A549). Organ cultures were preincubated with ADMA (0.1 to 4 × 10−4 M) or d-NMMA (2 × 10−4 M) for 30 min prior to bacterial infection. Infected organ cultures (8 h) had significantly (P ⩽ 0.05) greater epithelial damage and fewer ciliated and unciliated cells than did control cultures. There was an increased level of nitrite in the medium feeding infected organ cultures as compared with control cultures. ADMA significantly (P ⩽ 0.05) reduced both bacterially induced epithelial damage and loss of ciliated cells in a concentration-dependent manner. d-NMMA did not influence the effect of P. aeruginosa...