Lundberg J O, Weitzberg E, Rinder J, Rudehill A, Jansson O, Wiklund N P, Lundberg J M, Alving K
Dept of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Eur Respir J. 1996 Jul;9(7):1344-7. doi: 10.1183/09031936.96.09071344.
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.
一氧化氮（NO）存在于人类鼻腔气道中，主要来源于鼻窦。免疫组织化学研究和信使核糖核酸（mRNA）原位杂交表明，健康鼻窦上皮中组成性表达2型一氧化氮合酶（NOS）。我们通过研究鼻窦黏膜活检组织中L-精氨酸向L-瓜氨酸的酶促转化，进一步对鼻窦NOS活性进行了表征。在面部重建手术期间，从9名健康受试者获取上颌窦活检组织。此外，比较了9名对照者与5名接受高全身剂量糖皮质激素治疗患者的鼻腔NO浓度。最后，在6名健康受试者中研究了静脉输注L-精氨酸对鼻腔NO浓度的影响。在所有活检组织中均发现了不依赖Ca(2+)的NOS活性，且该活性比依赖Ca(2+)的活性高5倍（分别为179±64和36±17 pmol·g-1·min）。对照者（344±21十亿分之一（ppb））与接受类固醇治疗患者（342±36 ppb）的鼻腔NO水平无差异。静脉输注L-精氨酸后，鼻腔NO水平升高了35%。我们得出结论，健康鼻窦黏膜中的NOS活性主要不依赖Ca(2+)，且这种NOS不会被全身类固醇下调。此外，静脉输注L-精氨酸可增加体内鼻腔气道NO排泄，表明底物浓度在基础条件下是一个限速因素。这些发现进一步支持了鼻窦NOS与2型NOS相同或密切相关的观点；然而，其表达调控似乎与先前描述的该NOS同工型有根本不同。
