Effects of topical nasal decongestants, L-arginine and nitric oxide synthase inhibition, on nasal cavity nitric oxide levels and nasal cavity volume in man

The effects evoked by locally administered, clinically used topical nasal decongestants (phenylephrine, oxymetazoline, and naphazoline), L-arginine, the nitric oxide synthase inhibitor N-omega-nitro-L-arginine-methyl ester, histamine, and capsaicin on nitric oxide levels in nasal cavity air were investigated in healthy human volunteers. Nasal cavity air was either sampled continuously (0.7 l/min) or as a 20 mL bolus during 15 seconds and further analyzed using a chemiluminescence technique for detection of nitric oxide. The continuous sampling technique may represent nitric oxide excretion into the nasal cavity, whereas the bolus sampling technique rather represents nitric oxide concentration in the nasal cavity. Nasal cavity volume was measured in parallel using an acoustic rhinometer in order to evaluate any possible correlation between nasal cavity volume and nasal cavity nitric oxide levels. Moreover, changes in nasal cavity volume were analyzed after nasal administration of nitric oxide gas. Phenylephrine, oxymetazoline, and naphazoline given acutely significantly decreased nasal cavity nitric oxide concentration (approximate to 50%). Oxymetazoline caused the most long-lasting effect (>6 hours) which, however, subsided within 12 hours. The effect on nasal cavity nitric oxide excretion was much smaller (approximate to 15% decrease), for all decongestants as measured using the continuous sampling technique. Repeated administration of oxymetazoline, during a 10-day period, did not reduce basal nasal cavity nitric oxide concentration or excretion as measured 12 hours after the last administration. Phenylephrine and oxymetazoline significantly increased nasal cavity volume (by 30-60%). Both histamine (10 mg/mL) and capsaicin (10 mu g/mL) markedly reduced nasal cavity volume (80% and 33%); however, they did not affect nasal cavity nitric oxide concentration. The strong correlation between the increase in nasal cavity volume and the decrease in nasal cavity nitric oxide levels, after administration of nasal decongestants, may therefore be due not only to changes in nasal cavity volume, but rather to parallel phenomena. Saline, L-arginine (100 mg/mL), and N-omega-nitro-L-arginine-methyl ester (50 mg/mL) did not evoke any significant alterations in nasal cavity nitric oxide levels or in nasal cavity volume. Exogenous nitric oxide gas (up to 90 ppm) did not induce any significant changes in nasal cavity volume. We conclude that alpha-adrenoceptor agonists given acutely reduce nitric oxide levels in the nasal airways. These effects are reversible, however, even after 10 days of repeated topical administration. Nitric oxide levels in the nasal cavity are not influenced by intranasally administered L-arginine or a nitric oxide synthase inhibitor, suggesting a diffusion barrier in the nasal mucosa for these agents, and moreover, that most of the nitric oxide found in the nasal cavity is produced in the paranasal sinuses. Furthermore, the nasal vasculature is resistant to luminal nitric oxide, in contrast to what has been shown earlier for the lower airways, possibly to prevent congestion.