Endotoxin (Etx) induced lung protein leak and loss of endothelial dependent relaxation

Endotoxin injures pulmonary vascular endothelium as assessed by histology and increased protein permeability. We hypothesized that another endothelial function might also be impaired by endotoxin. Lung protein leak was measured in rats given S. enteriditis Etx ip (4 mg/kg) with extravascular (EV) protein accumulation derived from total lung radiolabelled protein (125I albumin) corrected for iv protein using 51Cr-RBC tag. Etx treated rats failed to show increased EV protein at 6 h after Etx but developed increased EV protein by 24 h. Endothelial dependent relaxation was assessed in rats using isolated pulmonary artery rings preconstricted with norepinephrine (10-7M). Endothelial dependent relaxation was induced by acetylcholine (10-6M, ACH) and calcium ionophore A23187 (10-6M,A23) and compared to endothelial independent relaxation with nitroprusside (10-7M, NP). Endothelial dependent relaxation was impaired only at 24 h. In conclusion, Etx induced a delayed pulmonary vascular endothelial injury in the rat as manifest by increased protein leak paralleled by diminished endothelial dependent relaxation