NASAL NITRIC-OXIDE CONCENTRATION IS DECREASED IN HEART-FAILURE PATIENTS RECEIVING NITRATES

Nitric oxide (NO) is a free radical gas and a short-lived messenger wh ich has many paracrine functions. Direct assessment of NO production i s very difficult in vivo. However, the paranasal cavities generate a h igh amount of NO which diffuses in the nasal cavity where it can be ea sily measured. Several studies have suggested alterations of the NO pr oduction in heart failure. Thus, we assessed nasal NO concentration in normal subjects and in heart failure patients. The nasal NO concentra tion averaged 227 +/- 10 ppb in the control group (n = 20), and 210 +/ - 10, 198 +/- 20 and 159 +/- 54 ppb in New York Heart Association (NYH A) class II (n = 30), III (n = 28) and IV (n = 7) patients, respective ly (mean +/- standard error [SE], not significant using analysis of va riance [ANOVA]). Nasal NO level was not influenced by age, sex or etio logy of the heart failure or by treatment with frusemide, angiotensin- converting enzyme inhibitor or digoxin. However, treatment with NO-rel easing drugs (nitrates or molsidomine) significantly decreased the nas al NO level in heart failure patients. A two-way ANOVA revealed that t reatment with a NO-releasing drug influenced nasal NO concentration (P = 0.0005), whereas NYHA class did not (P = 0.23), with a trend toward s an interaction between the two parameters (P = 0.09): the inhibitory effect of NO-releasing drug on nasal NO concentration was more pronou nced in severe heart failure. In an additional group of 12 patients (N YHA class IT or III), the nasal NO concentration was 174 +/- 19 ppb du ring NO-releasing drug treatment and increased to 231 +/- 27 ppb 3 day s after withdrawal of the nitrates (P = 0.0007 using paired t-test). C onversely, the nasal NO concentration in another group of seven patien ts (NYHA class II or III) was 219 +/- 32 ppb without nitrate treatment and decreased to 188 +/- 28 ppb 7 days after nitrate addition (P = 0. 02 using paired t-test). In contrast, the nasal NO concentration in an other group of ten ischemic patients without heart failure was 203 +/- 25 ppb without nitrate treatment and was similar (207 +/- 28 ppb) 7 d ays after nitrate addition (not significant using paired t-test). In c onclusion, nasal NO production is normal in heart failure, except in p atients receiving NO-releasing drugs. Nasal NO concentration could be useful for investigating the mechanism(s) by which exogenous NO donors decrease endogenous NO production. (C) 1998 Elsevier, Paris.