Inhibition of nitric oxide synthesis attenuates thermally induced asthma.
To determine whether the inhibition of nitric oxide (NO) synthesis attenuates thermally induced obstruction, we had 10 asthmatic volunteers perform isocapnic hyperventilation with frigid air after inhaling 1 mg of N(G)-monomethyl-L-arginine (L-NMMA) or isotonic saline in a blinded fashion. The challenges were identical in all respects, and there were no differences in baseline lung function [1-s forced expiratory volume (FEV(1)); saline 2.8 +/- 0.3 liters, L-NMMA 2.9 +/- 0.3 liters; P = 0.41] or prechallenge fractional concentration 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 impact on the FEV(1), pulse, or blood pressure. After L-NMMA, FENO fell significantly (P < 0.0001), the stimulus-response curves shifted to the right, and the minute ventilation required to reduce the FEV(1) 20% rose 53.5% over control (P = 0.02). The results of this study demonstrate that NO generated from the airways of asthmatic individuals may play an important role in the pathogenesis of thermally induced asthma.
Kotaru
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Airway Disease Center, Division of Pulmonary and Critical Care Medicine, University Hospitals of Cleveland, Ohio 44106, USA.
Skowronski
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Coreno
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A
McFadden
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ER
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001794:Blood Pressure; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006339:Heart Rate; D006439:Hemodynamics / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D006985:Hyperventilation; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011674:Pulse; D015656:Respiratory Mechanics / Q000502:physiology; D016037:Single-Blind Method; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase