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Endogenous nitric oxide is decreased in asthmatic patients by an inhibitor of inducible nitric oxide synthase. 1996

D H Yates, and S A Kharitonov, and P S Thomas, and P J Barnes
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.

Exhaled nitric oxide (NO) may be derived from constitutive NO synthase (NOS) in normal airways, but the increased concentration in asthma is likely to be derived from inducible NOS expressed in inflamed airways. To investigate this, we administered a nonselective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), and a selective inhibitor of inducible NOS, aminoguanidine, by nebulization in a double-blind, placebo-controlled manner in both normal subjects and subjects with asthma. L-NAME resulted in a significant reduction in exhaled NO compared with saline control in eight normal subjects (maximum fall from baseline, 53 +/- 7.6% versus 8.9 +/- 6.5%; P < 0.05) and in seven patients with asthma (maximum fall, 67 +/- 7.4% versus 10 +/- 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 (maximum fall, 28 +/- 9.3 versus 15 +/- 11). No rise in blood pressure, fall in FEV1, or adverse effects were observed in either subject group. We have demonstrated that NOS inhibitors can safely be given by inhalation in a single does in normal subjects and subjects with asthma. The raised exhaled NO concentration in patients with asthma may be attributable to induction of NOS, with that in normal subjects reflecting basal constitutive NOS activity.

UI MeSH Term Description Entries
D008297 Male Males
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D004311 Double-Blind Method A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D005260 Female Females
D005541 Forced Expiratory Volume Measure of the maximum amount of air that can be expelled in a given number of seconds during a FORCED VITAL CAPACITY determination . It is usually given as FEV followed by a subscript indicating the number of seconds over which the measurement is made, although it is sometimes given as a percentage of forced vital capacity. Forced Vital Capacity, Timed,Timed Vital Capacity,Vital Capacity, Timed,FEVt,Capacities, Timed Vital,Capacity, Timed Vital,Expiratory Volume, Forced,Expiratory Volumes, Forced,Forced Expiratory Volumes,Timed Vital Capacities,Vital Capacities, Timed,Volume, Forced Expiratory,Volumes, Forced Expiratory
D006146 Guanidines A family of iminourea derivatives. The parent compound has been isolated from mushrooms, corn germ, rice hulls, mussels, earthworms, and turnip juice. Derivatives may have antiviral and antifungal properties.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000280 Administration, Inhalation The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract. Drug Administration, Inhalation,Drug Administration, Respiratory,Drug Aerosol Therapy,Inhalation Drug Administration,Inhalation of Drugs,Respiratory Drug Administration,Aerosol Drug Therapy,Aerosol Therapy, Drug,Drug Therapy, Aerosol,Inhalation Administration,Administration, Inhalation Drug,Administration, Respiratory Drug,Therapy, Aerosol Drug,Therapy, Drug Aerosol
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001120 Arginine An essential amino acid that is physiologically active in the L-form. Arginine Hydrochloride,Arginine, L-Isomer,DL-Arginine Acetate, Monohydrate,L-Arginine,Arginine, L Isomer,DL Arginine Acetate, Monohydrate,Hydrochloride, Arginine,L Arginine,L-Isomer Arginine,Monohydrate DL-Arginine Acetate

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