Effect of different ozone concentrations on the neurogenic contraction and relaxation of guinea pig airways

Abstract

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.

Ozone induces impairment of adrenergic relaxation in thoracic guinea pig tracheas

“…This finding clarified our previous observation related to the apparent tendency of tracheas exposed to 1.2 ppm O 3 to relax less than the control tissues. 2 Our current results clearly point out that O 3 indeed causes a post-junctional impairment of the adrenergic relaxation, which is revealed only when thoracic trachea is used.…”

“…5 Mediators involved in these pathways include epinephrine and norepinephrine, as well as nitric oxide and vasoactive intestinal peptide, respectively. 6 In a previous work 2 we reported that O 3 induced an impairment of prejunctional adrenergic relaxation without affecting the post-junctional guinea pig tracheal responses to isoproterenol (ISO) and sodium nitroprusside (NP), a well-known nitric oxide donor. Interestingly, in that study we found a tendency of tracheas exposed to 1.2 ppm to relax less than control tissues.…”

“…Only a few of them try to explain the phenomenon through a derangement of relaxation pathways. [2][3][4] In guinea pig trachea, airway smooth-muscle relaxation is controlled by both adrenergic and non-adrenergic non-cholinergic pathways. 5 Mediators involved in these pathways include epinephrine and norepinephrine, as well as nitric oxide and vasoactive intestinal peptide, respectively.…”

Spontaneous changes in guinea‐pig respiratory pattern during barometric plethysmography: role of catecholamines and nitric oxide

“…These include sympathetic nervous system activation, glucocorticoid release and NO production (Li & Quock, 2002; Sanchez et al 2003; Shalev, 2002). In this context, catecholamines and NO are two well‐known relaxing agents of the airway smooth muscle (Hamad et al 2003; Sommer et al 1997). Because the combination of propranolol and l ‐NAME abolished the low basal airway tone at the beginning of the plethysmographic session, it is reasonable to suggest that this phenomenon was mediated by the stress‐induced release of catecholamines and NO.…”

Non-quantal release of acetylcholine in guinea-pig airways: role of choline transporter

“…Some experiments were conducted in a Ca 2+ ‐free medium (with 0.1 m m of the Ca 2+ chelator EGTA), and other experiments used electrical field stimulation (EFS) with square pulses of 16 Hz, 2 ms and 100 V for 10 s delivered through platinum electrodes. It has been shown that this EFS protocol produces a biphasic response, with an initial cholinergic contraction followed by an adrenergic and non‐adrenergic relaxation (Sommer et al 1997). Four initial EFSs were sequentially delivered 10 min apart in order to corroborate their repeatability.…”