Oxidant injury, nitric oxide and pulmonary vascular function: implications for the exercising horse

The athletic ability of the horse is facilitated by vital physiological adaptations to high-intensity exercise, including a thin (but strong) pulmonary blood-gas barrier, a large pulmonary functional reserve capacity and a consequent maximum oxygen uptake (VO2max) far higher than in other species. A high pulmonary artery pressure also serves to enhance pulmonary function, although stress failure of lung capillaries at high pulmonary transmural pressures, and the contribution of other factors which act in the exercising horse to increase pulmonary vascular tone, may lead to pathological or pathophysiological sequelae, such as exercise-induced pulmonary haemorrhage (EIPH). Reactive oxygen species (ROS) are an important component of the mammalian inflammatory response. They are released during tissue injury and form a necessary component of cellular defences against pathogens and disease processes. The effects of ROS are normally limited or neutralized by a multifactorial system of antioxidant defences, although excessive production and/or deficient antioxidant defences may expose healthy tissue to oxidant damage. In the lung, ROS can damage pulmonary structures both directly and by initiating the release of other inflammatory mediators, including proteases and eicosanoids. Vascular endothelial cells are particularly susceptible to ROS-induced oxidant injury in the lung, and both the destruction of the pulmonary blood-gas barrier and the action of vasoactive substances will increase pulmonary vascular resistance. Moreover, ROS can degrade endothelium-derived nitric oxide (NO), a major pulmonary vasodilator, thereby, with exercise, synergistically increasing the likelihood of stress failure of pulmonary capillaries, a contributing factor to EIPH. This review considers the implications for the exercising horse of oxidant injury, pulmonary vascular function and NO and the contribution of these factors to the pathogenesis of equine respiratory diseases.