Regulation of mucociliary motility by nitric oxide and expression of nitric oxide synthase in the human sinus epithelial cells

Objectives: This study was performed to investigate the changes in ciliary beat frequency (CBF) after treatment with L-arginine in the human sinus mucosa and to determine the distribution of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in the healthy sinus mucosa. Study Design/Methods: CBF was measured in the sphenoid sinus mucosa of 12 patients who underwent trans-septal trans-sphenoidal hypophysectomy for the treatment of pituitary gland tumor. CBF was measured over 24 hours in Dulbecco's modified Eagle's medium (DMEM) after treatment with L-arginine, its inactive spatial isomer D-arginine, or an NOS inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME). DMEM without treatment with these materials was used as a control. Other pieces of the mucosa were exposed to L-NAME and its inactive spatial isomer D-NAME after preincubation with L-arginine. The specimens were immunohistochemically stained for iNOS and eNOS. Results: CBF increased 24 hours after treatment with L-arginine as compared with control groups. CBF increased in proportion to the increasing concentrations of L-arginine. There was no significant change after treatment with D-arginine or L-NAME. CBF increased after treatment with L-arginine at 30 minutes and maintained for 24 hours. L-NAME inhibited the increase in CBF by L-arginine, but D-NAME showed no such effect. Immunoreactivity to both iNOS and eNOS was frequently observed in the ciliated epithelial cells and was stronger to eNOS than to iNOS. Conclusions: From the results of this study it is suggested that nitric oxide (NO) produced by iNOS and eNOS using L-arginine may increase CBF in the healthy sinus mucosa and that NO may have a regulatory function in ciliary motility in the human sinus mucosa.