Sommer B, Vargas M H, Segura P, Bazán-Perkins B, Carbajal V, Chávez J, Gustin P, Montaño L M
Departamento de Investigación en Asma, Instituto Nacional de Enfermedades Respiratorias, Tlalpan, México DF, México.
Fundam Clin Pharmacol. 1997;11(6):501-11. doi: 10.1111/j.1472-8206.1997.tb00854.x.
Prejunctional and postjunctional effects of several ozone (O3) concentrations, including those found in highly polluted cities, were evaluated in guinea pig airways. Animals bred in O3-free conditions were exposed to air or O3 (0.3, 0.6 or 1.2 ppm) during 4 h, and studied 16-18 h later. Tracheal and bronchial rings were studied in organ baths. Electrical field stimulation (EFS) (100 V, 2 ms, 10 s) was given at increasing frequencies (0.25-16 Hz). Some tissues received atropine (2 microM) and/or propranolol (10 microM). Concentration-response curves to carbachol, isoproterenol, nitroprusside, and substance P were constructed. In tracheas, almost all O3 concentrations decreased the relaxation at low EFS frequencies, but had no effect on the propranolol-resistant (i-NANC) relaxation, suggesting that only adrenergic relaxation was affected. This was a prejunctional effect, since O3 did not modify the responses to isoproterenol. Relaxation induced by a nitric oxide (NO) donor, nitroprusside, was not affected by O3, which agrees with the lack of O3-effect on i-NANC system. O3 did not modify the EFS-induced e-NANC contraction in atropine-treated bronchi, nor the contraction caused by exogenous substance P. By contrast, in bronchi without atropine, 1.2 ppm O3 increased the e-NANC contraction induced by the highest EFS (16 Hz). O3 increased the maximum responses to carbachol in tracheas (1.2 ppm) and bronchi (0.6 and 1.2 ppm). In conclusion, we found that: a) O3 decreased adrenergic relaxation in guinea pig tracheas at low EFS frequencies through a prejunctional alteration; b) O3 did not modify the i-NANC relaxation in tracheas, at least the NO-mediated; c) O3 added a cholinergic component to the bronchial slow-phase (e-NANC) contraction evoked by EFS; and d) O3 enhanced the cholinergic responses in trachea and bronchi by a postjunctional mechanism.
在豚鼠气道中评估了几种臭氧（O3）浓度（包括在高污染城市中发现的浓度）的接头前和接头后效应。在无O3条件下饲养的动物在4小时内暴露于空气或O3（0.3、0.6或1.2 ppm）中，并在16 - 18小时后进行研究。在器官浴中研究气管和支气管环。以递增频率（0.25 - 16 Hz）给予电场刺激（EFS）（100 V，2 ms，10 s）。一些组织接受阿托品（2 microM）和/或普萘洛尔（10 microM）。构建了对卡巴胆碱、异丙肾上腺素、硝普钠和P物质的浓度 - 反应曲线。在气管中，几乎所有O3浓度在低EFS频率下均降低了舒张反应，但对普萘洛尔抵抗性（i - NANC）舒张无影响，这表明仅肾上腺素能舒张受到影响。这是一种接头前效应，因为O3未改变对异丙肾上腺素的反应。一氧化氮（NO）供体硝普钠诱导的舒张不受O3影响，这与O3对i - NANC系统无作用一致。O3未改变阿托品处理的支气管中EFS诱导的e - NANC收缩，也未改变外源性P物质引起的收缩。相比之下，在未用阿托品的支气管中，1.2 ppm O3增加了由最高EFS（16 Hz）诱导的e - NANC收缩。O3增加了气管（1.2 ppm）和支气管（0.6和1.2 ppm）对卡巴胆碱的最大反应。总之，我们发现：a）O3通过接头前改变在低EFS频率下降低豚鼠气管中的肾上腺素能舒张；b）O3未改变气管中的i - NANC舒张，至少是NO介导的；c）O3在EFS诱发的支气管慢相（e - NANC）收缩中增加了胆碱能成分；d）O3通过接头后机制增强了气管和支气管中的胆碱能反应。
