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  • Title: Sodium metabisulfite and citric acid induce bronchoconstriction via a sulfite-sensitive pathway in the isolated guinea pig lung.
    Author: Atzori L, Bannenberg G, Corriga AM, Congiu L, Lundberg JM, Moldèus P, Ryrfeldt A.
    Journal: Respiration; 1997; 64(2):145-51. PubMed ID: 9097350.
    Abstract:
    Inhalation of sodium metabisulfite (MBS; 80 mM; pH 2.9 +/- 0.1) or citric acid (CA; 0.4 M; pH 2.0 +/- 0.1) aerosols induced a reduction in compliance and conductance in the isolated perfused and ventilated guinea pig lung without affecting perfusion flow. The effect was dependent on the pH of the nebulized solution since inhalation of 80 mM MBS aerosols at pH 7.4 did not induce any effect on bronchial tone. Concomitantly to the bronchoconstriction induced by MBS or CA an increased level of calcitonin gene-related peptide (CGRP-LI) in the effluent perfusate was observed, indicating activation of sensory nerves. Sodium sulfite, a dissolution product of MBS, has previously been shown by our studies to reduce bronchoconstriction induced by inhalation of sulfur dioxide, in the isolated perfused and ventilated guinea pig lung. In the present study perfusion of the lung with sodium sulfite (3 mM) before and during exposure to aerosols with either MBS or CA attenuated the bronchoconstriction induced by the acidic solutions. The release of CGRP-LI induced by MBS or CA was not affected by sodium sulfite. Sulfite treatment did not modify perfused guinea pig lung reactivity towards acetylcholine (4 nmol), bradykinin (100 pmol), histamine (10 nmol), serotonin (500 pmol) and substance P fragment 5-11, a substance P analogue resistant to degrading enzyme (500 pmol). However, an inhibitory effect by sodium sulfite was observed on bronchoconstriction induced by the NK-2 agonist neurokinin A fragment 4-10 (NKA 4-10, 25 pmol). These results indicate that MBS- or CA-induced bronchoconstriction was dependent on the low pH of the aerosol solution and coincided with activation of sensory nerves. Sulfite modulation of the bronchoconstricting action of inhaled MBS and CA is suggested to be related to a sulfite-sensitive step in the signal transduction of the neuropeptide NKA.
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