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The effect of the nitric oxide synthase inhibitor, L-NMMA, on sodium metabisulphite-induced bronchoconstriction and refractoriness in asthma.
Eur Respir J. 1999 Sep; 14(3):702-5.ER

Abstract

Refractoriness to indirect bronchoconstrictor stimuli, is a feature of asthma but the mechanism is poorly understood. This study tested the hypothesis that endogenous nitric oxide (NO) produced during a first bronchoconstrictor challenge protects against subsequent challenge and therefore has a role in the refractory process. The effect of an NO synthase inhibitor, N(G)-mono-methyl-L-arginine (L-NMMA), on refractoriness to sodium metabisulphite (MBS) was investigated in 20 subjects with mild asthma. On visit one, the dose of MBS which caused a 20% fall in forced expiratory volume in one second (FEV1) (PD20) was determined. On visit two, the refractory index (RI) to MBS was determined by challenging the subjects twice with their PD20 of MBS, the second challenge proceeding after recovery from the first. Those showing a refractory index of approximately 30% (10 subjects) inhaled either L-NMMA or placebo followed 5 min later by two challenges with their PD20 of MBS in a double-blind cross over study at two further visits. The dose of L-NMMA used was shown to reduce exhaled NO for a duration sufficient to cover the second MBS challenge However, no significant difference was found between L-NMMA and placebo in maximum fall in FEV1% and area under the curve (AUC) during first or second MBS challenges or in RI on the two study days. It is concluded that subjects with mild asthma show refractoriness to sodium metabisulphite, but that endogenous nitric oxide is unlikely to be involved either in the refractory process or in the response to sodium metabisulphite per se.

Authors+Show Affiliations

Dept of Respiratory Medicine, City Hospital, Nottingham, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10543296

Citation

Hamad, A M., et al. "The Effect of the Nitric Oxide Synthase Inhibitor, L-NMMA, On Sodium Metabisulphite-induced Bronchoconstriction and Refractoriness in Asthma." The European Respiratory Journal, vol. 14, no. 3, 1999, pp. 702-5.
Hamad AM, Wisniewski A, Range SP, et al. The effect of the nitric oxide synthase inhibitor, L-NMMA, on sodium metabisulphite-induced bronchoconstriction and refractoriness in asthma. Eur Respir J. 1999;14(3):702-5.
Hamad, A. M., Wisniewski, A., Range, S. P., Small, T., Holland, F., & Knox, A. J. (1999). The effect of the nitric oxide synthase inhibitor, L-NMMA, on sodium metabisulphite-induced bronchoconstriction and refractoriness in asthma. The European Respiratory Journal, 14(3), 702-5.
Hamad AM, et al. The Effect of the Nitric Oxide Synthase Inhibitor, L-NMMA, On Sodium Metabisulphite-induced Bronchoconstriction and Refractoriness in Asthma. Eur Respir J. 1999;14(3):702-5. PubMed PMID: 10543296.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of the nitric oxide synthase inhibitor, L-NMMA, on sodium metabisulphite-induced bronchoconstriction and refractoriness in asthma. AU - Hamad,A M, AU - Wisniewski,A, AU - Range,S P, AU - Small,T, AU - Holland,F, AU - Knox,A J, PY - 1999/10/30/pubmed PY - 1999/10/30/medline PY - 1999/10/30/entrez SP - 702 EP - 5 JF - The European respiratory journal JO - Eur Respir J VL - 14 IS - 3 N2 - Refractoriness to indirect bronchoconstrictor stimuli, is a feature of asthma but the mechanism is poorly understood. This study tested the hypothesis that endogenous nitric oxide (NO) produced during a first bronchoconstrictor challenge protects against subsequent challenge and therefore has a role in the refractory process. The effect of an NO synthase inhibitor, N(G)-mono-methyl-L-arginine (L-NMMA), on refractoriness to sodium metabisulphite (MBS) was investigated in 20 subjects with mild asthma. On visit one, the dose of MBS which caused a 20% fall in forced expiratory volume in one second (FEV1) (PD20) was determined. On visit two, the refractory index (RI) to MBS was determined by challenging the subjects twice with their PD20 of MBS, the second challenge proceeding after recovery from the first. Those showing a refractory index of approximately 30% (10 subjects) inhaled either L-NMMA or placebo followed 5 min later by two challenges with their PD20 of MBS in a double-blind cross over study at two further visits. The dose of L-NMMA used was shown to reduce exhaled NO for a duration sufficient to cover the second MBS challenge However, no significant difference was found between L-NMMA and placebo in maximum fall in FEV1% and area under the curve (AUC) during first or second MBS challenges or in RI on the two study days. It is concluded that subjects with mild asthma show refractoriness to sodium metabisulphite, but that endogenous nitric oxide is unlikely to be involved either in the refractory process or in the response to sodium metabisulphite per se. SN - 0903-1936 UR - https://www.unboundmedicine.com/medline/citation/10543296/The_effect_of_the_nitric_oxide_synthase_inhibitor_L_NMMA_on_sodium_metabisulphite_induced_bronchoconstriction_and_refractoriness_in_asthma_ L2 - http://erj.ersjournals.com/cgi/pmidlookup?view=long&pmid=10543296 DB - PRIME DP - Unbound Medicine ER -