Role of lung superoxide in the rapid cardiovascular dysfunction of acute endotoxemia

The generation of free radicals such as Superoxide is believed to be a major contributing factor to lung damage associated with acute endotoxemia. However, its role in the cardiovascular depression that occurs in acute endotoxemia has not been well characterized. We measured levels of lung Superoxide generation, 15 min after lipopolysaccharide (LPS)(10 mg/kg, salmonella enteritidis, i.v.) administration in instrumented, anesthetized rats. We also examined protein levels (as an index of capillary leakiness) and the number of macrophages in bronchoalveolar lavage (BAL). Timed controls were given saline. 15 min after LPS administration, there was a 12% drop in mean arterial blood pressure (MABP) compared to controls. Coincident with this drop, there was a two-fold increase in Superoxide generation in lung tissue. Protein levels were higher in BAL from LPS treated rats compared to controls. Surprisingly, there was a two-fold decrease in BAL macrophage numbers in LPS treated rats compared to controls. Thus, we show for the first time that Superoxide generated from lungs may have a direct effect on the rapid decrease in MABP which occurs in rats given LPS. The Superoxide may be derived from pulmonary macrophages and the decrease in BAL macrophages may reflect movement from alveolar space towards the vascular compartment.