The effect of platelet-activating factor (PAF) on nasal airway resistance in healthy subjects is not mediated by nitric oxide

Background: The nose is an important source of nitric oxide (NO) in man, bu t the relevance of NO production to the response to inflammatory mediators is not clear. Methods: In this study, we evaluated the effect of NO inhibition on nasal a irway resistance (NAR) at baseline, after an acute challenge with platelet- activating factor (PAF), a potent proinflammatory factor, and after an acut e challenge with bradykinin (BK), both of which are mediators of allergic r hinitis in man. Eight healthy subjects were enrolled in the study. Nasal NO production was measured by the chemiluminescence method, and NAR was measu red by active anterior rhinomanometry. Results: Basal nasal NO concentration was 500.6 +/- 115.6 ppb; it significa ntly decreased after topical administration of the NO-synthase inhibitor L- NAME, and the NO-synthase substrate L-arginine caused a recovery in NO prod uction. The administration of L-NAME did not cause any change in basal NAR. In a double-blind fashion, we pel formed nasal challenge with PAF and BK a fter topical pretreatment with either placebo or L-NAME. After placebo pret reatment, both PAI; and BK caused a significant increase in NAR(respectivel y from 0.29 +/- 0.11 Pa s cm(-3) to 0.75 +/- 0.21 Pa s cm(-3), and from 0.3 6 +/- 0.18 Pa s cm(-3) to 0.71 +/- 0.25 Pa s cm(-3); P < 0.001, n = 8). Pre treatment with L-NAME did not prevent the PAF-induced increase in NAR (from 0.31 +/- 0.10 Pa s cm(-3) to 0.71 +/-0.27 Pa s cm(-3)), whereas it prevent ed the BK-induced increase in NAR (from 0.33 +/- 0.15 Pa s cm(-3) to 0.33 /- 0.16 Pa s cm(-3)). Conclusions: Topical administration of the NO-synthase inhibitor L-NAME at doses sufficient to decrease NO nasal production does not prevent the PAF-i nduced increase in NAR, indicating that NO generation in vivo is not involv ed in the nasal response to PAF.