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Abstract
Nitric oxide (NO) is produced by a variety of cells within the respiratory tract,
particularly airway epithelial cells, and its increased concentration in asthma is
likely to derive from inducible NO synthase (iNOS) expressed in inflamed airways.
To evaluate whether an increased bronchial flux of NO (ie, airway wall NO flux [Jno]
in picoliters per second) produced in the large airways is due to an enzyme overexpression,
we administered a relatively selective iNOS inhibitor, aminoguanidine, by nebulization
in a double-blind, placebo-controlled manner in asthmatic and healthy subjects and
also investigated whether the same concentration of inhibitor has any effect on NO
produced in the peripheral lungs (ie, alveolar NO concentration [Calv] in parts per
billion [ppb]) or on the diffusing capacity of NO (Dno) [in picoliters per second(-1)
per ppb(-1)) in the airways. Aminoguanidine administration resulted in a significant
reduction in Jno compared with administration of the saline solution control in eight
healthy subjects and in eight patients with asthma but caused no significant changes
in Calv or in Dno in either group. No rise in BP, fall in FEV(1), or adverse effects
were observed in either group. These results indicate that iNOS from larger airways
is the predominant source of elevated large airway-derived NO in patients with asthma,
and that exhaled NO from peripheral lungs is not affected by a nebulized iNOS inhibitor
and, therefore, is more likely to be derived form constitutive forms of NO synthase.