Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Impaired Nitric Oxide Synthetase Activity in Primary Ciliary Dyskinesia – Data-Driven Hypothesis

Version 1 : Received: 4 August 2023 / Approved: 7 August 2023 / Online: 8 August 2023 (14:01:01 CEST)

A peer-reviewed article of this Preprint also exists.

Eggenkemper, L.; Schlegtendal, A.; Maier, C.; Lücke, T.; Brinkmann, F.; Beckmann, B.; Tsikas, D.; Koerner-Rettberg, C. Impaired Nitric Oxide Synthetase Activity in Primary Ciliary Dyskinesia—Data-Driven Hypothesis. J. Clin. Med. 2023, 12, 6010. Eggenkemper, L.; Schlegtendal, A.; Maier, C.; Lücke, T.; Brinkmann, F.; Beckmann, B.; Tsikas, D.; Koerner-Rettberg, C. Impaired Nitric Oxide Synthetase Activity in Primary Ciliary Dyskinesia—Data-Driven Hypothesis. J. Clin. Med. 2023, 12, 6010.

Abstract

Low nasal nitric oxide (nNO) is a typical feature in Primary Ciliary Dyskinesia (PCD). nNO is part of the PCD diagnostic algorithm due to its discriminative power against other lung diseases such cystic fibrosis (CF). However, the underlying pathomechanisms are elusive. To better understand NO dysregulation in PCD, the L-arginine/NO (Arg/NO) pathway in patients with PCD (pwPCD) and CF (pwCF) and in healthy control (HC) subjects was investigated. In a prospective, controlled study, we measured in 24 pwPCD, 25 age-matched pwCF, and 14 HC the concentrations of the NO precursors Arg and homoarginine (hArg), the arginase metabolite ornithine (Orn), the NO inhibitor asymmetric dimethylarginine (ADMA), and the major NO metabolites (nitrate, nitrite) in sputum, plasma and urine by validated methods. In comparison to HC, the sputum contents (in µmol/mg) of L-Arg (PCD 18.43 vs. CF 329.46 vs. HC 9.86, p < 0.001) and of ADMA (PCD 0.055 vs. CF 0.015 vs. HC 0.010, p < 0.001) were higher. In contrast, the sputum contents (in µmol/mg) of nitrate and nitrite were lower in PCD compared to HC (nitrite 4.54 vs. 9.26, p = 0.023; nitrate 12.86 vs. 40.33, p = 0.008), but higher in CF (nitrite 16.28, p <0.001; nitrate 56.83, p = 0.002). The metabolite concentrations in urine and plasma were similar in all groups. The results of our study indicate that PCD, unlike CF, is associated with impaired NO synthesis in the lung, presumably due to mechano-chemical uncoupling.

Keywords

primary ciliary dyskinesia; nitric oxide; nitric oxide synthetase; cystic fibrose; L-arginine

Subject

Medicine and Pharmacology, Pulmonary and Respiratory Medicine

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.