Inhibition of nitric oxide synthesis attenuates thermally induced asthma

To determine whether the inhibition of nitric oxide (NO) synthesis attenuat es thermally induced obstruction, we had 10 asthmatic volunteers perform is ocapnic hyperventilation with frigid air after inhaling 1 mg of N-G-monomet hyl-L-arginine (L-NMMA) or isotonic saline in a blinded fashion. The challe nges were identical in all respects, and there were no differences in basel ine lung function [1-s forced expiratory volume (FEV1); saline 2.8 +/- 0.3 liters, L-NMMA 2.9 +/- 0.3 liters; P = 0.41] or prechallenge fractional con centration of nitric oxide in the exhaled air (FENO) [saline 23 +/- 6 parts /billion (ppb), L-NMMA 18 +/- 4 ppb; P = 0.51]. Neither treatment had any i mpact on the FEV1, pulse, or blood pressure. After L-NMMA, FENO fell signif icantly (P < 0.0001), the stimulus-response curves shifted to the right, an d the minute ventilation required to reduce the FEV1 20% rose 53.5% over co ntrol (P = 0.02). The results of this study demonstrate that NO generated f rom the airways of asthmatic individuals may play an important role in the pathogenesis of thermally induced asthma.