ADENOSINE PREVENTS PERMEABILITY INCREASE IN OXIDANT-INJURED ENDOTHELIAL MONOLAYERS

Adenosine is thought to prevent or reduce the increase in permeability , which is a hallmark of oxidant injury to endothelium. However, the e ffect of adenosine on endothelial cells directly exposed to oxidant sp ecies has not been demonstrated in vitro. By measuring the passage of Evan's blue dye-labeled albumin across confluent monolayers, we demons trated the ability of adenosine (0.1-100 mu M) to lower basal permeabi lity of human umbilical vein endothelial cells in a concentration-depe ndent fashion and prevent the permeability increase induced by exposur e of the cells to xanthine plus xanthine oxidase (X/XO). Whereas pretr eatment of monolayers for 10 min with adenosine (10 and 100 mu M) prev ented the X/XO-induced permeability increase, these same concentration s of adenosine failed to increase intracellular adenosine 3',5'-cyclic monophosphate in X/XO-exposed cells. The protective effect of adenosi ne on endothelial monolayers was mimicked by adenosine amine congener and 5'-(N-ethylcarboxamido)adenosine but not by other agonists examine d. Hence, the protective effect of adenosine against oxidant injury ma y include an adenosine 3',5'-cyclic monophosphate-independent mechanis m by direct action of adenosine at A(1) receptors on endothelial cells .