Tetrahydrobiopterin attenuates modulation of platelet 12-lipoxygenase and cyclooxygenase activities by nitric oxide

Endothelial cells secrete large amounts of 5,6,7,8-tetrahydrobiopterin (BH, ) in septic conditions. BH4 is a cofactor for nitric oxide (NO) synthase an d an essential regulator of its activity. We recently showed that NO can be a modulator of both platelet 12-lipoxygenase and cyclooxygenase activities . In the present study, we investigated the effect of BH4 on the activities of la-lipoxygenase and cyclooxygenase in rabbit platelets. The influence o f BH4 on NO-induced modulation of these enzyme activities was investigated. Exogenous BH4 did not affect platelet 12-lipoxygenase and cyclooxygenase a ctivities. The modulatory effects of NO on the two enzymatic pathways were reversed by addition of BH4 but not by reduced glutathione. These results s uggest that exogenous BH, is not essential for NO synthase activity of plat elets, but that it is an important regulator of the action of NO released f rom other sources on platelet 12-lipoxygenase and cyclooxygenase activities . (C) 2001 Academic Press.