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 sin us epithelium. We have further characterized sinus NOS activity by stu dying the enzymatic conversion of L-arginine to L-citrulline in biopsi es from sinus mucosa Maxillary sinus biopsies were obtained from nine healthy subjects during reconstructive facial surgery, In addition, na sal NO concentrations in nine controls were compared with those found in five patients treated with high systemic doses of glucocorticostero ids. Finally, the effects of i.v. L-arginine infusion on nasal cavity NO concentrations were studied in six healthy subjects. Ca2+-independe nt NOS activity was found in all biopsies and was five times higher th an Ca2+-dependent activity (179+/-64 and 36+/-17 pmol . g(-1). min, re spectively). There was no difference in nasal NO levels between contro ls (344+/-21 parts per billion (ppb)) and steroid-treated patients (34 2+/-36 ppb). Nasal NO levels increased up to 35% following i.v. infusi on of L-arginine. We conclude that NOS activity in healthy sinus mucos a is predominantly Ca2+-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 concentrat ion is a rate-limiting factor under basal conditions. These findings f urther 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.