The effect of endogenous nitric oxide on cholinergic ciliary stimulation of human nasal mucosa

Abstract

Objectives/hypothesis: Endogenous nitric oxide (NO) production by inducible nitric oxide synthase is enhanced in the nasal ciliated respiratory tract epithelium of patients with allergic rhinitis. Recent experimental data have suggested endogenous NO to be strongly involved in the complex regulation of ciliary activity, the driving force of the mucociliary transport system. The authors investigated the effect of endogenous NO on acetylcholine-stimulated ciliary activity of human nasal mucosa.

Study design: In vitro study.

Methods: Cultures of human nasal mucosa explants were incubated with tumor necrosis factor-alpha and bacterial lipopolysaccharides to enhance endogenous NO production. Expression of inducible NO synthase was morphologically demonstrated by immunohistochemistry. Ciliary beat frequency was determined by phase-contrast microscopy of ciliated epithelium, using a computerized photoelectric technique. Stimulation experiments were performed in vitro with acetylcholine and N(G)-nitro-l-arginine methyl ester (L-NAME), a NO synthase inhibitor.

Results: Upregulation of inducible NO synthase in the respiratory tract epithelium after stimulation with tumor necrosis factor-alpha and lipopolysaccharide was visualized by immunohistochemical analysis. Experimental inhibition of enhanced endogenous NO production by 10 mol/L L-NAME significantly reduced baseline ciliary beat frequency from 8.6 +/- 0.2 to 7.8 +/- 0.2 Hz (P < .05). Cholinergic ciliary stimulation above baseline by 10 mol/L acetylcholine was not significantly different before (11.5%) or after (10.8%) blocking of endogenous NO production.

Conclusion: Taken together, the study results suggest that baseline ciliary activity depends on endogenous NO production but that the extent of cholinergic ciliary stimulation is independent of endogenous NO production. The combination of the two effects may improve nasal mucociliary clearance of inhaled allergens in patients with allergic rhinitis.