title: Inhibition of nitric oxide synthesis attenuates thermally induced asthma.
abstract: 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.
authors.affiliation: Airway Disease Center, Division of Pulmonary and Critical Care Medicine, University Hospitals of Cleveland, Ohio 44106, USA.
authors.forename: C
authors.initials: C
authors.lastname: Kotaru
authors.forename: M
authors.initials: M
authors.lastname: Skowronski
authors.forename: A
authors.initials: A
authors.lastname: Coreno
authors.forename: E R
authors.initials: ER
authors.lastname: McFadden
mesh_terms: 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*
chemical_list: D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase