Calcium-independent and steroid-resistant nitric oxide synthase activity in human paranasal sinus mucosa

Nitric oxide (NO) is present in the human nasal airways and originates primarily from the paranasal sinuses. Immunohistochemical studies and messenger ribonucleic acid (mRNA) in situ hybridization indicate that a type-2 NO synthase (NOS) is constitutively expressed in healthy sinus epithelium. We have further characterized sinus NOS activity by studying the enzymatic conversion of L-arginine to L-citrulline in biopsies from sinus mucosa. Maxillary sinus biopsies were obtained from nine healthy subjects during reconstructive facial surgery. In addition, nasal NO concentrations in nine controls were compared with those found in five patients treated with high systemic doses of glucocorticosteroids. Finally, the effects of i.v. L-arginine infusion on nasal cavity NO concentrations were studied in six healthy subjects. Ca(2+)-independent NOS activity was found in all biopsies and was five times higher than Ca(2+)-dependent activity (179 +/- 64 and 36 +/- 17 pmol.g-1.min, respectively). There was no difference in nasal NO levels between controls (344 +/- 21 parts per billion (ppb)) and steroid-treated patients (342 +/- 36 ppb). Nasal NO levels increased up to 35% following i.v. infusion of L-arginine. We conclude that NOS activity in healthy sinus mucosa is predominantly Ca(2+)-independent and this NOS is not downregulated by systemic steroids. Furthermore, L-arginine infusion increases nasal airway NO excretion in vivo, indicating that the substrate concentration is a rate-limiting factor under basal conditions. These findings further support the notion that sinus NOS is identical or very closely related to the type-2 NOS; however, the regulation of expression seems to be fundamentally different from that described previously for this NOS isoform.