Sulfur Dioxide and Sodium Metabisulfite Induce Bronchoconstriction in the Isolated Perfused and Ventilated Guinea Pig Lung via Stimulation of Capsaicin-Sensitive Sensory Nerves

Abstract

In this study the relationship between sulfur dioxide-induced sensory nerve activation and acute bronchoconstriction was assessed. We also studied the effects of sodium metabisulfite, an agent that is suggested to increase airway resistance via activation of sensory nerves. Sulfur dioxide (250 ppm) induced a characteristic biphasic bronchoconstriction. Concomitantly sulfur dioxide induced the release of calcitonin gene-related peptide (CGRP) from capsaicin-sensitive sensory nerves into the pulmonary circulation. In lungs of guinea pigs pretreated with a neurotoxic dose of capsaicin, the first phase of bronchoconstriction was reduced and the overflow of CGRP was not detectable. Tetrodotoxin abolished the initial phase of the bronchoconstriction induced by sulfur dioxide, indicating that a local neural reflex depending on sodium channels was operant. Inhibition of the vanilloid receptor with capsazepine slightly, although not significantly, reduced the contractile responses to sulfur dioxide. Sodium metabisulfite, when infused via the pulmonary circulation (3 mM), induced bronchoconstriction which was abolished by capsaicin pretreatment, but not significantly reduced by capsazepine. The results indicate that in the isolated guinea pig lung inhaled sulfur dioxide induces initial bronchoconstriction in part via sensory nerve activation, while other mechanisms are involved in the late effect. Sensory nerve activation appears to be the only mechanism for bronchoconstriction induced by infused sodium metabisulfite. A role for sensory nerve-mediated bronchoconstriction by sulfur dioxide or sodium metabisulfite via activation of the vanilloid receptor could not be conclusively demonstrated by this study using capsazepine.

Sodium Metabisulfite and Citric Acid Induce Bronchoconstriction via a Sulfite-Sensitive Pathway in the Isolated Guinea Pig Lung

“…Thus, the release of tachvkinins from sensory nerves is a possi ble mechanism by which inhaled MBS or CA causes bron choconstriction in our experimental model. Previous studies by our group support the hypothesis that in the isolated and ventilated guinea pig lung SO, inhalation and perfusion with MBS induce bronchoconstriction through release of tachvkinins [12,18].…”

“…Activation of neurokinin receptors on smooth muscle cells has been suggested to be responsible for the contrac tile response to MBS and CA [1,5,18]. The neurokinin receptors act through a G protein to cause IP3 production which in turn elevates cytoplasmic Ca2+ [26].…”

In vivo exposure to nitrogen dioxide (NO2) induces a decrease in calcitonin gene-related peptide (CGRP) and tachykinin immunoreactivity in guinea-pig peripheral airways

“…Similar experiments have shown changes in the rate of neuropeptide release with decreased nerve staining in the lung tissue following administration of the sensory irritant sulphur dioxide [29]. Release of tachykinins is also implied by the SP-mediated vasodilation and plasma extravasation caused by the gas phase of cigarette smoke, which itself has an appreciable concentration of NO 2 [30].…”

Short-Term Exposure to Diesel Exhaust Induces Nasal Mucosal Hyperresponsiveness to Histamine in Guinea Pigs

“…Capsaicin pretreatment inhibits the increase in vascular permeability and sneezing response induced by DEP (Kobayashi, unpublished data). It has been also shown that gaseous components, such as NO 2 (Lucchini et al, 1996), SO 2 (Bannenberg et al, 1994), and aldehyde such as acrolein (Springall et al, 1990) induced the release of SP and/or CGRP from sensory nerves. In die skin, it has been reported that CGRP (Brain and Williams, 1985) released from sensory nerves markedly enhanced edema induced by substances that increase vascular permeability.…”