OXIDANT INJURY, NITRIC-OXIDE AND PULMONARY VASCULAR FUNCTION - IMPLICATIONS FOR THE EXERCISING HORSE

The athletic ability of the horse is facilitated by vital physiologica l adaptations to high-intensity exercise, including a thin (but strong ) pulmonary blood-gas barrier, a large pulmonary functional reserve ca pacity and a consequent maximum oxygen uptake (VO2max) far higher than in other species. A high pulmonary artery pressure also serves to enh ance pulmonary function, although stress failure of lung capillaries a t high pulmonary transmural pressures, and the contribution of other f actors which act in the exercising horse to increase pulmonary vascula r tone, may lead to pathological or pathophysiological sequelae, such as exercise-induced pulmonary haemorrhage (EIPH). Reactive oxygen spec ies (ROS) are an important component of the mammalian inflammatory res ponse. They are released during tissue injury and form a necessary com ponent of cellular defences against pathogens and disease processes. T he effects of ROS are normally limited or neutralized by a multifactor ial 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 directl y and by initiating the release of other inflammatory mediators, inclu ding proteases and eicosanoids. Vascular endothelial cells are particu larly 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. Mor eover, ROS can degrade endothelium-derived nitric oxide (NO), a major pulmonary vasodilator, thereby, with exercise, synergistically increas ing the likelihood of stress failure of pulmonary capillaries, a contr ibuting factor to EIPH. This review considers the implications for the exercising horse of oxidant injury, pulmonary vascular function and N O and the contribution of these factors to the pathogenesis of equine respiratory diseases.