['Abrupt cessation of heparin therapy can lead to a recrudescence of thrombosis and acute ischemia. Endothelial NO is an important endogenous inhibitor of platelet-mediated thrombosis, yet biochemical studies examining the effect of heparin on NO production by the endothelium have heretofore been lacking.', 'In an attempt to address the effect of heparin on endothelial cell production of NO, confluent bovine aortic endothelial cells (BAECs) on microcarrier beads were incubated in the presence or absence of heparin. Results indicate that BAECs incubated with heparin were less able to inhibit platelet aggregation than control cells (P<.005 by ANOVA) and that this effect correlated with a decrease in NO production (36% decrease for heparin compared with control, P<.05). Dextran sulfate evoked the same response (67% decrease, P<.0001 compared with control), suggesting that the decrease in NO after heparin treatment is secondary to its negative charge rather than to a specific polysaccharide sequence. The decrease in NO production by heparin was accompanied by a 72% decrease in steady-state Nos 3 mRNA as well as a 49% decrease in immunodetectable endothelial NO synthase (eNOS) protein.'] Does high-dose heparin decrease nitric oxide production by cultured bovine endothelial cells?