Endothelial cells (EC) possess several protective thromboregulatory me
chanisms that may be perturbed by cell activation or injury. Vascular
ATP-diphosphohydrolase (ATPDase) has been demonstrated on both aortic
EC and smooth muscle cells and may play a key regulatory role in hemos
tasis and platelet reactivity by converting extracellular ATP and ADP
to AMP. We have examined the role of exogenous saturated or unsaturate
d fatty acids in the modulation of EC associated ATPDase activity in v
itro. EC growth was not dramatically influenced by supplementation wit
h fatty acids whereas viability was enhanced by oleic, butyrate and ei
cosapentaenoic acid. EC cultures supplemented with saturated or a mono
unsaturated (oleic acid) fatty acid(s) had markedly increased ATPDase
activity, whereas those exposed to polyunsaturated fatty acids showed
substantive decreases. Exogenous oleic acid could also protect against
the significant loss of ATPDase activity, following exposure to react
ive oxygen intermediates in vitro. We conclude that endothelial ATPDas
e activity may be regulated by exogenous fatty acids and that underlyi
ng mechanisms include alterations in the nature of the phospholipid co
mposition of EC membranes that influence responses to oxidative stress
reactions.