The inhibition of sodium influx attenuates airway response to a specific antigen challenge

Abstract

1 We have previously observed that manipulation of Na' availability during passive in vitro sensitization altered electrophysiological and contractile changes of airway smooth muscle cells.The purpose of this study was to establish whether interference with Na' influx during sensitization also influences the response of airway smooth muscle, both in vivo and in vitro, to a specific antigen challenge.2 Isolated segments of trachea which had been sensitized to ovalbumin in the presence of the Na' channel-blocking agent amiloride (10-M) showed no electrical or contractile response to ovalbumin in spite of their ability to respond to histamine (10-I M).3 Airway smooth muscle preparations sensitized to ovalbumin in a Na'-deficient medium failed to show any contractile response after exposure to ovalbumin and only a small depolarization of airway smooth muscle cells was detected. 4 Guinea-pigs were passively sensitized in vivo either in the absence of, or following pretreatment with, amiloride (1 mg kg-1 s.c.). These animals were then exposed to an ovalbumin inhalation challenge and both lung resistance (RL) and dynamic lung compliance (Cdy.) were measured.5 After an inhalation challenge of sensitized animals, we observed a significant increase in lung resistance (RL) achieving a maximum of 489% of the baseline values and a decrease in dynamic lung compliance (Cdyn). Twenty min after ovalbumin challenge Cdyf was equivalent to 20% of baseline values. 6 In animals pretreated with amiloride during sensitization, the inhalation challenge caused only a small increase in RL achieving a maximum increase of 148% of baseline values, and a small decrease in Cdy.. Twenty min after ovalbumin challenge Cdy. was equivalent to 98% of baseline values.7 We concluded that interference with Na' influx during both in vitro and in vivo sensitization attenuates the contractile and electrical responses of airway smooth muscle preparations or the changes in lung resistance and compliance observed after antigen challenge.

Association between Lung Function in Adults and Plasma DDT and DDE Levels: Results from the Canadian Health Measures Survey

“…DDT and related compounds are neurotoxicants that bind to voltage-gated sodium channels to prevent their closure, which leads to increased sodium influx and repeated firing of neurons ( Keifer and Firestone 2007 ). In addition, physiological studies of animal models have shown that sodium influx and subsequent depolarization of neurons in general can cause contractile responses of airway smooth muscles ( Souhrada and Souhrada 1989 ; Souhrada et al 1988 ). Moreover, DDT and its metabolite DDE have been shown to be able to activate stress-response signaling in vitro , including ERK/MAPK (extracellular-signal-regulated kinase/mitogen-activated protein kinase), JNK (c-Jun N-terminal kinase), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways, which results in an intracellular release of calcium ( Abdollahi et al 2004 ; Androutsopoulos et al 2013 ).…”

The alpha 1-adrenergic agonist methoxamine and the "loop" diuretic frusemide reduce nasal potential difference

“…At concentrations greater than 1 f,.lM, the drug selectively inhibits Na•JH• exchange at the apical surface of the epithelium [17] and in addition has been shown to affect a variety of other cellular functions in a range of tissues, including calcium influx in muscle and neuronal cells; at higher concentrations (> 1 mM) amiloride may also inhibit Na•tCa 2 • exchange [17,18]. Although the effect of amiloride on bronchial provocation in asthma is unknown, the drug reduces the airway response to antigen challenge in guinea-pigs pretreated with amiloride during sensitization [19], demonstrating that interference with epithelial Na• flux can modify the response to airway challenge in vivo. The frusemideand methoxamine-induced reduction in PD, therefore, suggests that either the transepithelial resistance was decreased by these drugs, or that active ion transport was reduced.…”

Methacholine, cold air and exercise challenge tests in the diagnosis of bronchial responsiveness at school age: A follow-up study from birth to school age

“…In bronchial challenge tests adaptable to children, the changes in air flow are usually demonstrated by peak expiratory flow (PEF) measurements, 1 although forced expiratory volume in 1 s (FEV 1 ) is the standard in adolescents and adults 1 . Methacholine or histamine, 2 cold air 3 and exercise 4 have been the most often used triggers in challenges.…”