ENDOGENOUS NITRIC-OXIDE IS DECREASED IN ASTHMATIC-PATIENTS BY AN INHIBITOR OF INDUCIBLE NITRIC-OXIDE SYNTHASE

Exhaled nitric: oxide (NO) may be derived from constitutive NO synthas e (NOS) in normal airways, but the increased concentration in asthma i s likely to be derived from inducible NOS expressed in inflamed airway s. To investigate this, we administered a nonselective NOS inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME), and a selective inhibitor of inducible NOS, aminoguanidine, by nebulization in a double-blind, p lacebo-controlled manner in both normal subjects and subjects with ast hma. L-NAME resulted in a significant reduction in exhaled NO compared with saline control in eight normal subjects (maximum fall from basel ine, 53 +/- 7.6% versus 8.9 +/- 6.5%; p < 0.05) and in seven patients with asthma (maximum fall, 67 +/- 7.4% versus 10 +/- 9.3%; p < 0.05). Aminoguanidine at the same molar concentration decreased exhaled NO in subjects with asthma (maximum fall, 53 +/- 7.2% versus 7.1 +/- 10.4%; p < 0.05), but caused no significant change in normal volunteers (max imum fall, 28 +/- 9.3 versus 15 +/- 11). No rise in blood pressure, fa ll in FEV(1), or adverse effects were observed in either subject group . We have demonstrated that NOS inhibitors can safely be given by inha lation in a single dose in normal subjects and subjects with asthma. T he raised exhaled NO concentration in patients with asthma may be attr ibutable to induction of NOS, with that in normal subjects reflecting basal constitutive NOS activity.