Nitric Oxide is a Regulator of Mucociliary Activity in the Upper Respiratory Tract

Abstract

The in vitro effects of the nitric oxide (NO) substrate L-arginine on ciliary beat frequency and the in vivo effects of the NO donor sodium nitroprusside (SNP) on mucociliary activity were investigated in the rabbit maxillary sinus mucosa with photoelectric techniques. L-Arginine increased ciliary beat frequency in vitro with a maximum response of 27.1% +/- 6.4% at 10(-3) mol/L, and this effect was reversibly blocked by pretreatment with the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine, whereas D-arginine had no such effect. SNP increased mucociliary activity in vivo, the peak response of 36.8% +/- 4.2% being obtained at the dose of 30.0 microg/kg. No tachyphylaxis was observed after repeat challenge with SNP. The increase in mucociliary activity caused by SNP was largely unaffected by pretreatment with the calcium channel blocker nifedipine, the cyclooxygenase inhibitor diclofenac, and the cholinergic antagonist atropine. The nonselective beta-blocker propranolol delayed the peak response of SNP to 7 to 8 minutes after challenge, compared with 1 to 2 minutes after challenge in animals without pretreatment. The results show the NO substrate L-arginine and the NO donor SNP to have ciliostimulatory effects in vitro and in vivo, respectively. The occurrence of NOS production in the sphenopalatine ganglion and sinus mucosa of the rabbit was studied by immunohistochemistry for NOS activity or nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry. The latter is an indirect sign of neuronal NOS activity. Numerous NOS-containing cell bodies were seen in the sphenopalatine ganglion; in the sinus mucosa a moderate supply of thin NOS-immunoreactive nerve fibers was seen. Taken together, the morphologic findings and the functional results indicate NO to be a regulator of mucociliary activity in upper airways.

Arginase Isoform Expression in Chronic Rhinosinusitis

“…NO is part of the first-line host defense mechanisms; its high concentration in the paranasal sinuses can reach up to 23.000 ppb [10], ensuring an antibacterial, antiviral, and antifungal effect. NO increases mucociliary clearance by upregulating ciliary motility; an association between low levels of NO and impaired mucociliary transport has been established [23,24]. Importantly, nitric oxide can display a pro- or anti-inflammatory effect conditioned by the type and phase of airway inflammation, its local concentration, and the individual response [25].…”

Nitric Oxide: A Promising Methodological Approach in Airway Diseases

“…The low levels of nasal NO in PCD may be due to several possible reasons – primarily, impaired NO synthesis. As already mentioned, it has been shown that the application of NO donors into the human nasal mucosa stimulates ciliary beat [98], and that low NO levels result in an impaired muco-ciliary function in the upper airways [19,99]. In fact, Loukides et al [100] demonstrated that in patients with PCD, L -arginine (a substrate for NO production) induced an increase in nasal NO levels, as well as improved ciliary beating frequency and nasal mucociliary clearance.…”

Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling

“…[4][5][6][7][8] Based on the recent advances in single-cell RNA-sequencing it became evident that more than one BC type exists in the airways and BC signature varies in different organs. [14][15][16][17] In the human upper airways nitric oxide released in response to taste receptor (TasR) stimulation increases ciliary beat, [18][19][20][21] but there is no proof that the same mechanism operates in the lower airways or additional mechanisms are influencing MC. 7,12 Yet, it remains elusive if these cells indeed synthesize and release ACh.…”

“…13 Cholinergic signaling is important for several innate immune processes in the airways, including MC. [14][15][16][17] In the human upper airways nitric oxide released in response to taste receptor (TasR) stimulation increases ciliary beat, [18][19][20][21] but there is no proof that the same mechanism operates in the lower airways or additional mechanisms are influencing MC. However, cholinergic signaling is important for other innate immune responses in the upper airways, since activation of solitary chemosensory cells (SCC) leads to cholinergic-mediated neurogenic inflammation in the nose.…”