Exhaled nitric oxide after inhalation of isotonic and hypotonic solutions in healthy subjects.

Airway nitric oxide (NO) homoeostasis is in¯uenced by chemical and mechanical stimuli in humans; airway epithelium, which is an important site of NO production, is sensitive to osmotic challenge. The effect of inhaled hypotonic solutions on exhaled NO (eNO) is not known. In this study we evaluated the effect of ultrasonically nebulized distilled water (UNDW), a hypotonic indirect stimulus, on eNO levels. A total of 10 non-smoking healthy subjects were enrolled in the study. eNO was detected by chemiluminescence, and speci®c airway conductance (sGaw) was measured by plethysmography. Bronchial challenges with UNDW and with an isotonic solution were performed according to a double-blind experimental design. Baseline levels of eNO were 28.1³14.7 p.p.b. UNDW did not cause any signi®cant change in sGaw (from 0.190³0.029 to 0.181³0.036 cmH2O[s−1). With respect to baseline values, the eNO concentration decreased signi®cantly after inhalation of 8 or 16 ml of UNDW (from 26.0³13.1 to 17.2³8.5 and 16.6³7.7 p.p.b. respectively; P!0.001, n¯10). After bronchial challenge with UNDW, eNO was signi®cantly reduced in comparison with after inhalation of the isotonic solution. In ®ve subjects, pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor NO synthesis, decreasedNOlevels from 21.7³8.5 to 10.0³3.3 p.p.b. Subsequent inhalation of 16 ml of UNDW did not cause any further decrease in NO levels (10.1³3.7 p.p.b. ; not signi®cant compared with L-NAME). We conclude that inhalation of aqueous solutions decreases eNO levels in healthy subjects, and that this effect is not associated with any signi®cant change in airway calibre. The UNDW-induced decrease in eNO is not enhanced by pretreatment with the NO synthase inhibitor L-NAME, suggesting that inhaled solutions may interfere with the airway NO pathway in humans.