Adenosine prevents permeability increase in oxidant-injured endothelial monolayers

Adenosine is thought to prevent or reduce the increase in permeabilty that is a hallmark of oxidant injury to endothelium We studied permeability changes of human umbilical vein endothelia! cells (HUVEC) by measuring the clearance of Evan's blue dye conjugated albumin (EBalb) across monolayers grown on cell culture inserts (3 μm pore size). Adenosine (1.0 μM -100 μM) decreased basal permeability of HUVECs in a concentration-dependent manner. The effect of adenosine on HUVEC monolayers exposed to xanthine/xanthine oxidase (X/XO) was also examined. Clearance of EB-alb was measured at 15, 30, 60, and 90 min following oxidant insult. Exposure to 200 μM X + 30 mU/ml XO caused a significant increase in permeability as early as 15 min. Pretreatment of monolayers for 10 min with 100 μM adenosine prevented the permeability increase. These data support the hypothesis that adenosine protects against oxidant injury by tightening the endothelial barrier and may prevent or reduce increased-permeability edema Supported by NIH HL43253. Clearance of Evan's Blue-Albumin, μl (mean ± sem) 15 min 30 min 60 min No treatment 41 ±6 74 ±5 90 ±4 X + XO 108 ±9 137 ±8 147±7 Adenosine + X + XO 33 ±4 60 ±7 67±15.