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, but 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 airway resistance (NAR) at baseline, after an acute challenge with platelet-activating factor (PAF), a potent proinflammatory factor, and after an acute challenge with bradykinin (BK), both of which are mediators of allergic rhinitis in man. Eight healthy subjects were enrolled in the study. Nasal NO production was measured by the chemiluminescence method, and NAR was measured by active anterior rhinomanometry.


RESULTS
Basal nasal NO concentration was 500.6+/-115.6 ppb; it significantly decreased after topical administration of the NO-synthase inhibitor L-NAME, and the NO-synthase substrate L-arginine caused a recovery in NO production. The administration of L-NAME did not cause any change in basal NAR. In a double-blind fashion, we performed nasal challenge with PAF and BK after topical pretreatment with either placebo or L-NAME. After placebo pretreatment, both PAF and BK caused a significant increase in NAR (respectively, from 0.29+/-0.11 Pa s cm(-3) to 0.75+/-0.21 Pa s cm(-3), and from 0.36+/-0.18 Pa s cm(-3) to 0.71+/-0.25 Pa s cm(-3); P<0.001, n=8). Pretreatment 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 prevented the BK-induced increase in NAR (from 0.33+/-0.15 Pa s cm(-3) to 0.43+/-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-induced increase in NAR, indicating that NO generation in vivo is not involved in the nasal response to PAF.
Maniscalco
M
M
Department of Respiratory Medicine, University Federico II, Naples, Italy.
Sofia
M
M
Faraone
S
S
Carratù
L
L
D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D015508:Nasal Obstruction / Q000139:chemically induced* / Q000378:metabolism; D009299:Nasal Provocation Tests; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000494:pharmacology*
D010972:Platelet Activating Factor; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester