Effects of Various Reactive Oxygen Species on the Guinea Pig Trachea and Its Epithelium

Abstract

ABSTRACT-Reactive oxygen species (ROS) are key factors playing important roles in tissue damage of airways under different pathological conditions. Effects of ROS (superoxide anion, H2O2 and hydroxyl radical) were recorded on isometric tension of intact and epithelium denuded, not precontracted guinea pig trachea. Superoxide anion was produced by xanthine /xanthine oxidase and hydroxyl radical either by FeSO4/H2O2 or FeSO4/ascorbic acid. In intact preparations, the muscle tension was unaffected by superoxide anion, while H 2 O 2 and hydroxyl radical produced a biphasic response, contraction followed by relaxation. Both the amplitude and duration of contractions evoked by H 2 O 2 were larger than those caused by hydroxyl radical producing systems. On denuded tracheal strips, superoxide anion elicited also a biphasic response, and the H 2 O 2 and hydroxyl radical produced contractions were of higher amplitude and of longer duration than in intact tissues. Indomethacin pretreatment enhanced or slightly reduced the amplitude of contractions evoked by both H 2 O 2 and hydroxyl radical on the intact and denuded preparations, respectively. Moreover, the duration of contractions of the trachea induced by oxidative systems was prolonged. Indomethacin did not affect the action of superoxide anion on the intact tissues and reduced the amplitude of the biphasic response on denuded ones. Nordihydroguaiaretic acid pretreatment did not alter the responses elicited by ROS in intact preparations and reduced their action on the denuded ones. Our results suggest that a) various ROS contract tracheal smooth muscle with simultaneous release of epithelium derived relaxing factors, b) epithelium possesses superoxide anion scavenging capacity which is high enough to protect smooth muscle from its actions, and c) cyclooxygenase products participate in relaxation and lipoxygenase products in contraction caused by ROS in the guinea pig trachea.

A Guinea Pig Model of Airway Smooth Muscle Hyperreactivity Induced by Chronic Allergic Lung Inflammation: Contribution of Epithelium and Oxidative Stress

“…Indeed, Mátyás et al (2002) showed that superoxide anion, hydroxyl radicals, and hydrogen peroxide cause the tracheal smooth muscle to contract, the latter being the ROS responsible for the greatest increase in muscle tone. In addition, the effects of these free radicals are contained by antioxidant defenses present in the intact epithelium, and epithelial damage potentiates the contractile effect of these ROS.…”

NADPH Oxidase-Derived ROS Induced by Chronic Intermittent Hypoxia Mediates Hypersensitivity of Lung Vagal C Fibers in Rats

“…Recent studies have reported that excess ROS may sensitize C-fiber afferents, which in turn leads to the development of airway hypersensitivity (Tsai et al, 2006 , 2009 ; Shen et al, 2012 ; Ruan et al, 2014 ) and thus ROS are likely to be the major mediators responsible for the CIH-induced consequences observed in this study. Additionally, excessive ROS may promote the release of other mediators such as cyclooxygenase metabolites and ATP (Chakraborti et al, 1989 ; Matyas et al, 2002 ; Tsai et al, 2009 ) within the airways, many of which are also able to sensitize airway C-fiber afferents (Ho et al, 2000 ; Gu et al, 2003 ; Tsai et al, 2009 ). Capsaicin, adenosine, and α,β-methylene-ATP are agonists of TRPV1, adenosine A1, and P2X receptors, respectively, which are located at the terminals of the LVCFs (Lin et al, 2009 , 2013 ).…”