Role of Endogenous Nitric Oxide in Airflow Obstruction in Smokers (Introduction)

10 Dec

Role of Endogenous Nitric Oxide in Airflow Obstruction in Smokers (Introduction)Objective: The aim of this study was to examine the relationship between endogenous nitric oxide (NO) level and airflow obstruction in smokers using single-breath measurement of exhaled NO with the sequential breath-holding method.
Setting: A university hospital.
Patients: Nine nonsmoking and ten smoking healthy volunteers.
Measurements: NO in exhaled air was measured using a chemiluminescence analyzer. Pulmonary function tests were performed using an autospirometer.

Results: The level of exhaled NO was higher in nonsmokers than in smokers, and the difference became larger as the breath-holding time increased. To evaluate the correlation between endogenous NO level and the degree of airflow obstruction in smokers, we used a new parameter, the NO concentration difference (ANO). Our findings indicate that reduced level of NO in exhaled air is an indicator of decreased NO synthesis within the respiratory system and is associated with the development of airflow obstruction in smokers (r=0.678; p<0.01).

Conclusions: ANO is a good indicator of the synthesis of endogenous NO within the respiratory system, and it appears likely that the reduced synthesis of NO may be a contributing factor to airflow obstruction in smokers. Nitric oxide (NO) is a ubiquitous gaseous free radical that acts as an intracellular messenger with a range of regulatory roles in different cells. Synthesis of NO, which is catalyzed by a specialized NO synthase using L-arginine as the substrate, has now been shown to take place in many types of cells.2 In the lungs, endogenous NO regulates pulmonary vascular function, and inhalation of exogenous NO can prevent pulmonary hypertension in humans as well as methacholine-induced bronchoconstriction in experimental animals. Production of NO, thus far, has been difficult to measure directly in vivo, although the end products of its metabolism, including nitrite and nitrate in plasma or urine, can be measured in some cases. However, it was recently shown that NO, which is probably formed within the respiratory system, can be found in parts per billion (ppb) levels in exhaled air of humans. This finding is of great importance to investigation of the physiologic roles of endogenous NO in the respiratory tract, since NO can be measured directly in exhaled air.

In humans, it has been demonstrated by single-breath measurement that the concentration of endogenous NO increases during breath-holding and that it is lower in smokers than in nonsmoking control subjects. However, to our knowledge, the physiologic effects of reduced levels of endogenous NO in exhaled air of smokers have not yet been studied. There is ample evidence that the airways of smokers react to nonspecific stimuli by undergoing constriction, which results in increased airway resistance, but the precise mechanism responsible for this reaction remains unknown. The aim of the present study was to evaluate the relationship between endogenous NO level and airflow obstruction in smokers using single-breath measurement of NO in exhaled air.