Origin of nitrite and nitrate in nasal and exhaled breath condensate and relation to nitric oxide formation.
BACKGROUND
Raised concentrations of nitrate and nitrite have been found in exhaled breath condensate (EBC) in airway disease, and it has been postulated that this reflects increased nitric oxide (NO) metabolism. However, the chemical and anatomical origin of nitrate and nitrite in the airways has not yet been sufficiently studied.


METHODS
The fraction of exhaled NO at an exhalation flow rate of 50 ml/s (FE(NO)) and nitrite and nitrate in EBC, nasal condensate, and saliva were measured in 17 tracheostomised and 15 non-tracheostomised subjects, all of whom were non-smokers without respiratory disease. Tracheal and oral samples were taken from the tracheostomised subjects and nasal (during velum closure) and oral samples from the non-tracheostomised subjects. Measurements were performed before and after sodium nitrate ingestion (10 mg/kg) and use of antibacterial mouthwash (chlorhexidine 0.2%).


RESULTS
In tracheostomised subjects oral FE(NO) increased by 90% (p<0.01) while tracheal FE(NO) was not affected 60 minutes after nitrate ingestion. Oral EBC nitrite levels were increased 23-fold at 60 minutes (p<0.001) whereas the nitrite levels in tracheal EBC showed only a minor increase (fourfold, p<0.05). Nitrate was increased the same amount in oral and tracheal EBC at 60 minutes (2.5-fold, p<0.05). In non-tracheostomised subjects oral FE(NO) and EBC nitrite increased after nitrate ingestion and after chlorhexidine mouthwash they approached baseline levels again (p<0.001). Nasal NO, nitrate, and nitrite were not affected by nitrate intake or mouthwash. At baseline, mouthwash with deionised water did not affect nitrite in oral EBC or saliva, whereas significant reductions were seen after antibacterial mouthwash (p<0.05 and p<0.001, respectively).


CONCLUSIONS
Besides the salivary glands, plasma nitrate is taken up by the lower airways but not the nasal airways. Nitrate levels in EBC are thus influenced by dietary intake. Nitrate is reduced to nitrite by bacterial activity which takes place primarily in the oropharyngeal tract of healthy subjects. Only oropharyngeal nitrite seems to contribute to exhaled NO in non-inflamed airways, and there is also a substantial contribution of nitrite from the oropharyngeal tract during standard collection of EBC.
Marteus
H
H
Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Törnberg
D C
DC
Weitzberg
E
E
Schedin
U
U
Alving
K
K
D000328:Adult; D000368:Aged; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D001944:Breath Tests; D002710:Chlorhexidine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009067:Mouthwashes / Q000494:pharmacology; D009566:Nitrates / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis* / Q000378:metabolism; D009666:Nose / Q000737:chemistry; D012463:Saliva / Q000737:chemistry; D014139:Tracheostomy
D000891:Anti-Infective Agents, Local; D009067:Mouthwashes; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; C031618:sodium nitrate; D002710:Chlorhexidine
Eur J Med Res. 2003 Nov 12;8(11):505-10
14644706
Bull Environ Contam Toxicol. 2004 Jan;72(1):109-13
15058661
Nat Rev Microbiol. 2004 Jul;2(7):593-602
15197394
Food Cosmet Toxicol. 1976 Dec;14(6):549-52
1017770
Cancer Res. 1983 Apr;43(4):1921-5
6831427
J Appl Biochem. 1985 Apr;7(2):86-92
3840469
Biochem Biophys Res Commun. 1991 Dec 16;181(2):852-7
1721811
Lancet. 1993 Dec 18-25;342(8886-8887):1510-3
7504773
Eur Respir J. 1993 Oct;6(9):1368-70
7507065
Compend Suppl. 1994;(18):S711-3; quiz S714-7
8039210
Eur Respir J. 1994 Aug;7(8):1501-4
7957837
Thorax. 1999 Dec;54(12):1061-9
10567624
Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):694-9
10712309
Eur Respir J. 2000 May;15(5):955-7
10853865
Respir Med. 2001 Feb;95(2):153-8
11217912
Am J Respir Crit Care Med. 2001 Mar;163(4):854-8
11282756
Thorax. 2001 Jun;56(6):456-61
11359961
Respir Med. 2001 Aug;95(8):649-54
11530952
Am J Respir Crit Care Med. 2002 Mar 1;165(5):663-9
11874811
Eur Respir J. 2002 Mar;19(3):487-91
11936527
Biomarkers. 2002 Jan-Feb;7(1):1-32
12101782
Ear Nose Throat J. 2002 Sep;81(9):659-61
12353444
Adv Drug Deliv Rev. 2002 Dec 5;54(11):1425-43
12458153
Nitric Oxide. 2003 Feb;8(1):26-30
12586538
Lancet. 1995 Nov 4;346(8984):1235-6
7475695
Nat Med. 1995 Jun;1(6):546-51
7585121
Am J Respir Crit Care Med. 1996 Jul;154(1):124-9
8680667
Clin Physiol. 1996 Jul;16(4):369-79
8842573
Arch Dis Child. 1996 Oct;75(4):323-6
8984919
Urology. 1997 Aug;50(2):189-91
9255286
Pediatr Pulmonol. 1997 Sep;24(3):173-7
9330413
Nitric Oxide. 1998;2(1):1-7
9706737
J Clin Invest. 1998 Sep 15;102(6):1200-7
9739054
Thorax. 1998 Aug;53(8):680-4
9828856
Eur Respir J. 1999 Feb;13(2):327-33
10065676
Eur Respir J. 1999 Jun;13(6):1402-5
10445619
Ann Rheum Dis. 2004 Dec;63(12):1649-54
15547090
Toxicol Appl Pharmacol. 2003 Apr 1;188(1):59-68
12668123
Chest. 2003 Aug;124(2):633-8
12907553
Chest. 2003 Sep;124(3):1046-52
12970036
Am J Med Sci. 2003 Oct;326(4):174-8
14557729