The effect of ozone on reactivity of upper and lower airways in guinea‐pigs

Abstract

The effect of ozone inhalation on the responsiveness of upper and lower airways to histamine was examined in guinea‐pigs. The exposure of conscious guinea‐pigs to 3.5 p.p.m. ozone for 30 min rendered their lower airways 2–3 fold more sensitive to the bronchoconstrictor action of i.v. histamine, as assessed subsequently under anaesthesia. The development of lower airway hyperreactivity was not modified by bilateral cervical vagotomy or pretreatment with BW 755C, FPL 55712 or SC‐39070. Under the conditions used, ozone exposure produced a mild inflammatory response as monitored by bronchoalveolar lavage, characterized by epithelial damage and prostaglandin E2 generation, but no cellular infiltration or oedema. In contrast to the lower airways, upper airway resistance was reduced by i.v. histamine. This response was not affected by ozone exposure. Isolated tracheal preparations taken from ozone‐exposed guinea‐pigs were not significantly more sensitive to histamine than control tissues. The mechanism of hyperreactivity in this model is unknown but does not depend on leukotriene generation or a vagal reflex.

Effect of oxidant air pollutants on the respiratory system: insights from experimental animal research

“…A reversible increase in airway responsiveness to several contractile agents is observed in animals after acute exposure to a concentration of O 3 ranging 0.5-3 ppm [35,38,[43][44][45][46][47][48][49][50][51][52]. Increased airway responsiveness to histamine has also been reported following exposure to 4 ppm or higher concentrations of NO 2 in guinea-pigs [53][54].…”

“…However, in guinea-pigs exposed to O 3 . the development of lower airway hyperresponsiveness to intravenous administration of histamine is not suppressed by bilateral cervical vagotomy or by inhibitors of arachidonic acid metabolism [52], and thus noncholinergic components may also mediate the hyperresponsiveness to histamine.…”

Dexamethasone inhibits ozone‐induced gene expression of macrophage inflammatory protein‐2 in rat lung

“…This effect has also been observed in dogs [3], guinea pigs [4] and rats [5]. Airway hyper-reactivity induced by ozone exposure is associated with epithelial injury [5][6][7][8] and an influx of inflammatory cells, mainly neutrophils [6,9,10].…”

Lack of local neurogenic involvement in the hyperreactivity induced by epithelium removal in guinea pig trachea

“…Most of these reports postulated that the loss of an epithelium-derived relaxant factor is the main mechanism accounting for the enhanced smooth muscle reactivity to agonists when epithelial layer is stripped off. Local axon reflex through afferent receptors exposure has also been suggested as another mechanism involved [4,16]. If this last consideration is true, it can be expected that blockade of neural transmission will reduce the hyperreactivity induced by epithelium loss.…”

“…Although this possibility has been outlined previously [4,16], as far as we know it has not been demonstrated experimentally in in vitro conditions. Therefore, in order to explore the role of local axon reflex and the involvement of airway wall ganglia in the hyperreactivity induced by epithelium removal, we investigated the effect of drugs affecting nervous conduction or ganglionic transmission in isolated epithelium-denuded guinea pig tracheas.…”