Abstract
Background: Nitric oxide (NO) is low in Primary Ciliary Dyskinesia (PCD) and has been found to be correlated with Ciliary Beat Frequency (CBF). Although low nasal NO is used in PCD diagnosis, few studies have examined the potentially therapeutic effect of increasing endogenous NO. We aimed to examine the effect of increasing NO production substrate L-Arginine, on CBF in human respiratory ciliated epithelium.
Methods: 27 suspect cases referred for PCD testing and 7 healthy controls underwent nasal brushing. The cells obtained were divided between solutions containing medium 199 with different L-Arginine levels (baseline: 0.33mM, 1mM and 10mM). CBF measurements were obtained at 37°C and at 1, 3 and 24 hours after brushing.
Results: PCD was confirmed in 8 subjects and excluded in 19. Among the PCD subjects, ciliary motility was characterized by rotational (n=5) or dyskinetic (n=3) beating. Compared to baseline, higher levels of L-Arginine resulted in up to 8.3% CBF increase at 1 hour (p=0.009), up to 9.6% CBF increase at 3 hours (p<0.001) and up to 12.5% CBF increase at 24 hours (p<0.001)(Fig.1). The effect of L-Arginine was similar in the three groups (interaction p=0.782) and it was time dependent (interaction p=0.002).
Conclusions: L-Arginine increases CBF and merits to be evaluated as a potential therapeutic agent for mucociliary clearance disorders with residual motility. Larger animal and human studies are needed.
- Copyright ©the authors 2016