Oxygen Radicals Produce Airway Constriction and Hyperresponsiveness in Anesthetized Cats

Abstract

Using 30 anesthetized cats, we examined whether oxygen radicals produce airway constriction or hyperresponsiveness. In one group, we administered aerosolized xanthine (0.1%) for 3 min followed by aerosolized xanthine oxidase (XO) (1 U/ml) for 5 min in order to generate oxygen radicals enzymatically in the airways. Pulmonary resistance (RL) instantaneously increased from 14.8 +/- 0.9 to 30.8 +/- 1.4 cm H2O/L/s (p less than 0.01). The increase in RL was significantly depressed by prior administration of polyethylene glycol-superoxide dismutase (PEG-SOD) or polyethylene glycolcatalase (PEG-CAT). In a second group, in order to examine changes in airway responsiveness, we studied acetylcholine (ACh) challenge before and 30, 60, and 120 min after inhalations of xanthine and XO. After xanthine-XO, the airways were hyperresponsive to ACh at 30 and at 60 min (p less than 0.05) but not at 120 min. The geometric means of ACh provocative concentrations that caused an increase in RL of 10 cm H2O/L/s above the baseline value before and 30, 60, and 120 min after xanthine-XO were 0.25, 0.045, 0.073, and 0.15%, respectively. The increase in responsiveness to ACh was significantly correlated with the increase in RL after xanthine-XO inhalation (r = 0.88, p less than 0.05). These data support the concept that oxygen radicals generated by xanthine-XO inhalation may induce bronchoconstriction and airway hyperresponsiveness.

Bronchial Hyperreactivity in the Peripheral Airways.

“…These studies have demonstrated the increase in inflammatory cells such as neutrophils and eosinophils associat-ed with the development of airway hyperresponsiveness (Holtzman et al 1983;Murphy et al 1986;Gundel et al 1990). Inflammatory cells produce oxygenderived free radicals which have been suggested to be related to the development of bronchial hyperreactivity (Katsumata et al 1990) and inactivation of proteolytic enzyme by oxidation (Dusser et al 1989). Thus, the inactivation of enzymes by the inflammation may provide a new mechanism of bronchial hyperresponsiveness in bronchial asthma.…”

Inhibitory effect of salmeterol on the respiratory burst of adherent human neutrophils

“…The activation of recruited neutrophils by locally generated mediators, including formyl peptides produced by proliferating bacteria [2] and eukaryotic mitochondria [3], leads to the release of histotoxic compounds such as enzymes and oxidants [4]. Other than causing tissue injury, neutrophil oxidants are presently thought to be involved in the pathogenesis of airway hyperreactivity and/ or bronchoconstriction [5,6]. As in other neutrophilic inflammatory processes, the extent of the neutrophil activation and, in turn, the generation of oxidants are down-regulated by endogenous mediators, mainly circulating catecholamines [7,8] and locally produced prostaglandins such as PGE 2 [9], via augmentation of intracellular levels of cyclic AMP (cAMP).…”

Obesity, Diet, Exercise and Asthma in Children

“…Increased ROS generation is found when the activity of neutrophils, eosinophils, monocytes and macrophages is increased, as occurs in asthma (Kelly et al, 1988). Oxidative stress (a situation of imbalance between the production of ROS and the ability to detoxify the reactive intermediates or to repair the resulting damage) is an important consequence of asthma inflammation; is associated with an altered activity in anti-oxidation in lungs and blood; and also with airway reactivity (Katsumata et al, 1990;Nadeem et al, 2005;Sackesen et al, 2008). There are numerous reports showing deficiencies of antioxidants in asthma: low levels of vitamin C in airway lining fluid, serum, plasma, whole blood and brochoalveolar lavage fluid; vitamin E in brochio-alveolar lavage fluid, red cells and plasma; or beta-carotene in serum (Kalayci et al, 2000;Kelly et al, 1999;Sackesen et al, 2008;Shanmugasundaram et al, 2001;Vural & Uzun, 2000;Wood et al, 2008).…”