Preventive effect of phosphoenolpyruvate on hypoxemia induced by oleic acid in Guinea pigs

Oleic acid-induced hypoxemia is an animal model of acute respiratory distress syndrome (ARDS). Increased capillary permeability is a cause of hypoxemia in lung injury. Endothelial cells form a major capillary barrier, and disruption of the barrier appears to involve a decreased level of ATP in the cells. Phosphoenolpyruvate (PEP) is an endogenous substance that is one of the ATP precursors and can cross some cell membranes via anion exchanger. We examined the effect of PEP on oleic acid-induced lung injury in guinea pigs. An intravenous injection of oleic acid (15 microl/kg) caused severe hypoxemia. Pretreatment with PEP at a dose of 2, 20, or 200 micromol/kg attenuated the oleic acid-induced decrease in the arterial partial pressure of oxygen in a dose-dependent manner. Furthermore, PEP attenuated the oleic acid-induced increase in vascular permeability in the proximal and distal bronchi, as indicated by the extravascular leakage of Evans Blue dye. The combination of PEP with ATP (4 micromol/kg) showed no additional inhibitory effect on oleic acid-induced lung injury, compared with PEP alone. We suggest that PEP is a promising candidate to prevent hypoxemia in acute lung injuries associated with increased vascular permeability, such as ARDS.