Bronchoconstriction induced by inhaled sodium metabisulfite in the guinea pig. Effect of capsaicin pretreatment and of neutral endopeptidase inhibition.
Sodium metabisulfite (MBS), a commonly used preservative, induces bronchoconstriction in asthmatics, probably through the release of sulfur dioxide (SO2). The mechanisms involved in MBS- and SO2-induced bronchoconstriction are not yet certain. We aerosolized MBS or acid control solution (pH, 2.7) to anesthetized, tracheostomized guinea pigs pretreated intravenously with propranolol (1 mg/kg). MBS was given at increasing doubling concentrations (0.01, 0.02, 0.04, and 0.08 M) every 5 min. Steep concentration-response curves were observed, and most animals responded at 0.02 or 0.04 M. Tachyphylaxis was seen at high concentrations and during a subsequent MBS challenge 15 min later. For pharmacologic studies, we stopped the challenge when lung resistance (RL) had increased by at least 350%; a second challenge was found to be reproducible. MBS response was measured as the concentration needed to increase RL by 350% (PC350). Atropine (1 mg/kg given intravenously) did not affect PC350 or the peak RL response. Inhibition of neutral endopeptidase by inhaled phosphoramidon (7.5 nmol) administered before the repeated challenge did not alter PC350 value to MBS or peak RL responses (phosphoramidon, 201 +/- 49% of first peak; vehicle, 164 +/- 35%). In addition, the increase in RL was not prolonged in the phosphoramidon-treated group. Animals treated subcutaneously with capsaicin (50 mg/kg) 1 wk before the experiment, so as to deplete neuropeptides from airway sensory nerves, had PC350 values similar to those of the control animals. Our data demonstrate that inhaled MBS causes bronchoconstriction in guinea pigs by mechanisms that are due neither to a cholinergic reflex nor to the release of tachykinins from airway sensory nerves.
Lötvall
J O
JO
Department of Thoracic Medicine, National Heart and Lung Institute, Brompton Hospital, London.
Skoogh
B E
BE
Lemen
R J
RJ
Elwood
W
W
Barnes
P J
PJ
Chung
K F
KF
D000336:Aerosols; D000818:Animals; D001980:Bronchi / Q000294:innervation; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010592:Pharmaceutic Aids; D011292:Premedication; D013447:Sulfites / Q000633:toxicity*; D013618:Tachyphylaxis
D000336:Aerosols; D006020:Glycopeptides; D010592:Pharmaceutic Aids; D013447:Sulfites; C005200:sodium metabisulfite; D015260:Neprilysin; D002211:Capsaicin; C008890:phosphoramidon