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Ozone and allergen exposure exacerbates the role of 5‐HT heteroreceptors in cholinergic mediated airway smooth muscle contraction in a non‐human primate model

Exposure of adolescent rhesus monkeys to ozone (O3) and/or house dust mite allergen (HDMA) has been shown to contribute to post natal remodeling of the neural, muscular and immunological components of the airway. Similar exposure regimens have associated O3 and HDMA with airway hyper responsiveness. One possible mechanism contributing to the increase in contractility has been attributed to the post‐ganglionic, pre‐synaptic influence of serotonin (5‐HT) on cholinergic mediated airway smooth muscle contraction. Twenty‐four adolescent rhesus monkeys were exposed to 11 episodes of filtered air (FA), HDMA aerosol, O3, or HDMA + O3 (5 days each followed by 9 days of FA). Ozone was delivered for 8 h/day at 0.5 ppm. All monkeys were sensitized to HDMA and were exposed to HDMA aerosol for 2 h/day on days 3‐5 of either FA (n = 6) or O3 (n = 6) exposure. Necropsies were performed at one year of age and 6 conducting airway rings were harvested for evaluation by electrical field stimulation. All four treatment groups exhibited an increase in contractility when exposed to increasing concentrations of 5‐HT (1uM‐100uM). The O3 treated group exhibited the greatest increase in contraction tension in response to 5‐HT (433% of control). Further evaluation of contractility utilizing specific 5‐HT receptor agonists revealed that the 5‐HT3 receptor subtype played a prominent role in exacerbating the cholinergic mediated contraction in the O3 treated group. The influence of 5‐HT3 receptors was also substantiated due to the attenuation of 5‐HT modulated contraction with the addition of a 5‐HT3 receptor antagonist.