In an animal model, nitric oxide (NO) has been shown to increase mucociliary activity in vivo and ciliary beat frequency in vitro. The aim of the present study was to investigate the effects of NO on blood flow and mucociliary activity in the human nose. The concentration of NO in nasal air was measured with a chemiluminescence technique after nebulizing the NO donor sodium nitroprusside (SNP) at a dose of 3.0 mg into the nose in six volunteers, and was found to increase by 50.1% ± 10.0% (mean ± SEM; p <.001) after the SNP challenge. Blood flow measured by laser Doppler flowmetry increased by 67.3% ± 15.5% (p <.05) after challenge with SNP at 1.0 mg, and by 75.4% ± 18.5% at 3.0 mg (p <.01; n = 6). The higher dose, which produced no subjective side effects, was then used in the mucociliary experiments. The maximum increase in nasal mucociliary activity was 57.2% ± 6.7% at 3.0 mg of SNP (n = 5). The findings support the view that NO regulates mucociliary activity and blood flow in the human nasal mucosa.
JainBRubinsteinIRobbinsRALeiseKLSissonJH. Modulation of airway epithelial cell ciliary beat frequency by nitric oxide. Biochem Biophys Res Commun1993; 191: 83–8.
2.
LundbergJONWeitzbergENordvallSLKuylenstiemaRLundbergJMAlvingK. Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome. Eur Respir J1994; 7: 1501–4.
3.
AfzeliusB. A human syndrome caused by immotile cilia. Science1976; 193: 317–9.
4.
AubersonSLacroixJSMorelDRLehmannWLundbergJM. Methylene blue attenuates vasodilatation and enhances vasoconstriction in response to endothelin-1 in the pig nasal mucosa. Acta Physiol Scand1991; 142: 149–56.
5.
SchmidtHWalterU. NO at work. Cell1994; 78: 919–25.
6.
LindbergSRunerT. Method for in vivo measurement of mucociliary activity in the human nose. Ann Otol Rhinol Laryngol1994; 103: 558–66.
7.
RunerTLindbergSMerckeUOlssonP. Effects of substance P and methacholine on mucosal blood flow in the upper airways. Am J Rhinol1995; 9: 335–45.
8.
LundbergJONFarkas-SzallasiTWeitzbergE. High nitric oxide production in human paranasal sinuses. Nature Med1995; 1: 370–3.
9.
KukovetzWHolzmannSSchmidtK. Cellular mechanisms of action of therapeutic nitric oxide donors. Eur Heart J1991; 12(suppl E): 16–24.
10.
RongenGASmitsPThienT. Characterization of ATP-induced vasodilation in the human forearm vascular bed. Circulation1994; 90: 1891–8.
11.
WeitzbergE. Circulatory responses to endothelin-1 and nitric oxide with special reference to endotoxin shock and nitric oxide inhalation. Acta Physiol ScandSuppl1993(suppl 611).
12.
LindbergSDolataJMerckeU. Mucociliary activity and the diving reflex. Am J Otolaryngol1990; 11: 182–7.
13.
IgnarroL. Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol1990; 30: 535–60.
14.
CervinABendeMLindbergSMerckeUOlssonP. Relations between blood flow and mucociliary activity in the rabbit maxillary sinus. Acta Otolaryngol (Stockh) 1988; 105: 350–6.
15.
RamisILorenteJRoselló-CafatauJQuesadaPGelpiEBulbenaO. Differential activity of nitric oxide synthase in human nasal mucosa and polyps. Eur Respir J1996; 9: 202–6.
16.
FurchgottRFZawadzkiJV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature1980; 288: 373–6.
17.
ZawadzkiJVFurchgottRFCherryP. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by substance P [Abstract]. Fed Proc1981; 40: 689.
18.
PalmerRMJFerrigeAGMoncadaS. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature1987; 327: 524–6.
19.
De NucciGThomasRD'Orleans-JusteP. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci USA1988; 85: 9797–800.
20.
HybbinetteJCMerckeU. Effects of the parasympathomimetic drug methacholine and its antagonist atropine on mucociliary activity. Acta Otolaryngol (Stockh) 1982; 93: 465–73.
21.
LindbergSHybbinetteJ-CMerckeU. Effects of neuropeptides on mucociliary activity. Ann Otol Rhinol Laryngol1986; 95: 94–100.
AmbleFRLindbergSOHMcCaffreyTVRunerT. Mucociliary function and endothelins 1, 2, and 3. Otolaryngol Head Neck Surg1993; 109: 634–45.
24.
JainBRubinsteinIRobbinsRSissonJ. TNF-α and IL-1β upregulate nitric oxide—dependent ciliary motility in bovine airway epithelium. Am J Physiol1995; 268: L911–L917.
25.
TamaokiJChiyotaniAKondoMKonnoK. Role of NO generation in β-adrenoceptor—mediated stimulation of rabbit airway ciliary motility. Am J Physiol1995; 268: C1342–C1347.
26.
MancinelliRLMcKayCP. Effects of nitric oxide and nitrogen dioxide on bacterial growth. Appl Environ Microbiol1983; 46: 198–202.
27.
CroenKD. Evidence for an antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication. J Clin Invest1993; 91: 2446–52.
