L-arginine reverses cigarette-induced reduction of fractional exhaled nitric oxide in asthmatic smokers.
BACKGROUND
Complex mechanisms regulate nitric oxide (NO) synthesis. Cigarette smoking decreases fractional exhaled NO (FE(NO)), while asthmatic inflammation increases FE(NO). To assess whether the smoking-induced decrease in FE(NO) levels was reversible, asthmatic and non-asthmatic smokers inhaled the NO synthase (NOS) substrate, L-arginine. Aminoguanidine, a relatively selective Type II NOS inhibitor, was used also to assess the role of NOS subtypes in these changes of FE(NO).


METHODS
The study was a single-blinded, placebo-controlled, cross-over design in two parts. Part I: smoking asthmatic and non-asthmatic smoking subjects smoked one cigarette and then inhaled nebulised L-arginine or L-alanine (control). Spirometry, FE(NO), nasal NO (FN(NO)), FE(CO), were measured for 4 h. Part II: subjects inhaled nebulised aminoguanidine prior to an identical protocol as in Part I. Change in FE(NO) was assessed as area under the curve (AUC).


RESULTS
Part I: In asthmatic smokers, cigarette smoking followed by L-arginine caused a significant median increase in AUC of 29.2(17)% FE(NO) change/hour (p = 0.04), which did not occur in non-asthmatic smokers (baseline FE(NO) 12.7(7.1-18) vs. 6.7(4-9.2) ppb, respectively). Part II: Aminoguanidine prior to smoking caused a significant fall in FE(NO) in both asthmatic and non-asthmatic smokers. L-arginine showed significant reversal of this effect in both asthmatic and non-asthmatic subjects.


CONCLUSIONS
In asthmatic smokers, L-arginine increases FE(NO) after cigarette smoking but not in non-asthmatic smokers. The decrease in FE(NO) after aminoguanidine and subsequent partial reversal by L-arginine in both groups, suggests that Type II NOS contributes to the FE(NO) in both.
Centre for Infection and Inflammation Research and POWH Clinical School, Faculty of Medicine , University of New South Wales, Randwick, NSW, Australia.
C T
CT
Bruce
D
D
Zhao
D H
DH
Yates
Paul S
PS
Thomas
D000328:Adult; D001120:Arginine / Q000008:administration & dosage*; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D001944:Breath Tests / Q000379:methods; D018592:Cross-Over Studies; D045853:Exhalation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000032:analysis*; D016037:Single-Blind Method; D012907:Smoking / Q000009:adverse effects / Q000188:drug therapy* / Q000503:physiopathology; D013147:Spirometry / Q000379:methods; D055815:Young Adult
D009569:Nitric Oxide; D001120:Arginine