Isoproterenol Ameliorates hyperoxia-induced Lung Dysfunctions and Injuries

Abstract

Background and objective: Hyperoxic acute lung injury is characterized by oxidative stress and inflammatory response, leading to endothelial and epithelial cell death. The temporal relationship between oxidative stress and respiratory dysfunction/injuries needs to be clarified. Methods: The progression of lung dysfunction (ventilation and blood gas) as well as injuries (oxidative and inflammatory) following hyperoxia were determined and the effects of antioxidant (vitamin C) and adrenoceptor agonist (isoproterenol) on the hyperoxia (48h)-challenged male Sprague-Dawley rats (8-10 wk) were tested. Results: Normobaric hyperoxia caused significant oxidative damages as determined by NADPH-dependent superoxide anion (O2(superscript •-)) production, antioxidant enzyme glutathione peroxidase (GPx), and malondialdehyde (MDA) at 24h post-hyperoxia. Respiratory functions (ventilation and blood oxygen) did not alter significantly except that airway resistance (higher Penh value) increased at this time point. At 48h post-hyperoxia, oxidative damages were no longer apparent, however, all respiratory functions were impaired significantly. Morphological changes including tissue swelling was also observed. In a separate experiment, pretreatment of vitamin C, isoproterenol, or saline followed by hyperoxia was performed. We found that isoproterenol, but not vitamin C was effective in ameliorating the hyperoxia-induced respiratory dysfunction, impairment of gas exchange, as well as tissue swelling. Conclusions: We have tested a model for defining time course of hyperoxia-induced respiratory dysfunction, oxidative stress, and lung injuries. Isoproterenol was found effective in improving these conditions and thus indicate that adrenoceptor-mediated events, in addition to oxidative stress, may play a significant role in hyperoxia-induced respiratory dysfunction and injuries.