O3-induced airway hyperresponsiveness to noncholinergic system and other stimuli

Abstract

The effect of O3 exposure (3 ppm, 1 h) on the in vivo and in vitro airway responsiveness, as well as the changes in cell contents in bronchoalveolar lavage (BAL) fluid, were evaluated 16-18 h after O3 exposure in sensitized and nonsensitized male guinea pigs. The sensitization procedure was performed through repeated inhalation of ovalbumin for 3 wk. Increase in pulmonary insufflation pressure produced by the excitatory nonadrenergic noncholinergic (eNANC) system, histamine, and antigen were assessed in in vivo conditions, whereas airway responsiveness to histamine and substance P was evaluated in in vitro conditions by use of tracheal chains with or without epithelium and lung parenchymal strips. We found that O3 exposure 1) increased the neutrophil content in BAL fluids in both sensitized and nonsensitized guinea pigs, 2) caused hyperresponsiveness to eNANC stimulation in nonsensitized guinea pigs (although combination of sensitization and O3 exposure paradoxically abolished the hyperresponsiveness to eNANC stimulation), 3) increased the in vivo bronchoconstrictor responses to histamine and antigen, 4) caused hyperresponsiveness to substance P in nonsensitized tracheae with or without epithelium and in sensitized tracheae with epithelium, 5) did not modify the responsiveness to histamine in tracheae with or without epithelium (and in addition, epithelium removal caused hyperresponsiveness to histamine even in those tracheae exposed to O3), and 6) produced hyperresponsiveness to histamine in lung parenchymal strips either from sensitized or nonsensitized guinea pigs.

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

“…Moreover, as reported above, when they are exposed after sensitization, the response to airway challenge occurs at lower antigen doses [49,51]. Facilitation of sensitization to ovalbumin has also been reported after exposure to 40 ppm NO 2 [150].…”

“…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].…”

“…The response to platinum, ovalbumin and Ascaris is enhanced by O 3 in platinum-sensitized monkeys, ovalbumin-sensitized guinea-pigs and Ascaris-sensitized dogs, respectively, [48][49][50][51]. Like the hyperresponsiveness to intravenous histamine, the increase in airway responsiveness to Ascaris antigen induced by ozone in Ascaris suum allergic dogs is not inhibited by the thromboxanesynthase inhibitor OKY-046, suggesting that thromboxane may not be involved [48].…”

“…Inflammation is a common feature of the lung response to a variety of environmental noxious agents, and has been noted in many species after exposure to O 3 or NO 2 [49,65,81,82,[91][92][93][94][95].…”

Ozone et réactivité bronchique : effet sur le muscle lisse des voies aériennes

“…-82-L'ozone entraîne également une augmentation du contrô le autonome non adréner gique, non cholinergique excitate ur (NANC ) [7]. Une partie de cet effet pourrait être liée à une diminu tio n du catabolisme des neuropeptides transmetteurs du système NANC par diminution d'activité de l'enzym e endopeptidase neutre, présente en grande quantité au niveau de l'épit hélium bronchique, une cible de l'effet toxique de 0 3 (7).…”