Complex mechanisms regulate nitric oxide (NO) synthesis. Cigarette smoking decreases fractional exhaled NO (FENO), while asthmatic inflammation increases FENO. To assess whether the smoking-induced decrease in FENO 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 FENO.
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, FENO, nasal NO (FNNO), FECO, were measured for 4 h. Part II: subjects inhaled nebulised aminoguanidine prior to an identical protocol as in Part I. Change in FENO was assessed as area under the curve (AUC).
Part I: In asthmatic smokers, cigarette smoking followed by l-arginine caused a significant median increase in AUC of 29.2(17)% FENO change/hour (p = 0.04), which did not occur in non-asthmatic smokers (baseline FENO 12.7(7.1–18) vs. 6.7(4–9.2) ppb, respectively).
Part II: Aminoguanidine prior to smoking caused a significant fall in FENO in both asthmatic and non-asthmatic smokers. l-arginine showed significant reversal of this effect in both asthmatic and non-asthmatic subjects.
In asthmatic smokers, l-arginine increases FENO after cigarette smoking but not in non-asthmatic smokers. The decrease in FENO after aminoguanidine and subsequent partial reversal by l-arginine in both groups, suggests that Type II NOS contributes to the FENO in both.
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The authors wish to thank the subjects for their participation. Supported by NH&MRC, Australia.
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Bruce, C.T., Zhao, D., Yates, D.H. et al. l-Arginine reverses cigarette-induced reduction of fractional exhaled nitric oxide in asthmatic smokers. Inflammopharmacol 18, 9–16 (2010). https://doi.org/10.1007/s10787-009-0017-9
- Cigarette smoking
- Nitric oxide