l-Arginine reverses cigarette-induced reduction of fractional exhaled nitric oxide in asthmatic smokers

Abstract

Introduction

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.

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, 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).

Results

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.

Conclusions

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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Acknowledgments

The authors wish to thank the subjects for their participation. Supported by NH&MRC, Australia.

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Correspondence to Paul S. Thomas.

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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

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Keywords

  • Aminoguanidine
  • Asthma
  • Cigarette smoking
  • Nitric oxide