TETRAHYDROBIOPTERIN IS A SECRETORY PRODUCT OF MURINE VASCULAR ENDOTHELIAL-CELLS

Tetrahydrobiopterin (BH4) is an obligatory cofactor of nitric oxide sy nthase and an essential regulator of its activity. The murine vascular endothelial cell line send1 constitutively secretes large amounts of BH4 as well as scant amounts of neopterin, an oxidized intermediate in the de novo biosynthesis of BH4. Further enhancement of BH4 and neopt erin secretion is achieved by activation with endotoxin (LPS) and inte rferon-gamma. This finding is in accordance with previous described BH 4 secretion by human endothelial cells. It supports the view that endo thelial cells are the source of BH4 serving vascular needs in vivo. In septic conditions, BH4 released by endothelial cells in large amounts could serve induced nitric oxide synthase in smooth muscle cells, the reby acting as another endothelium-derived relaxing factor mediating v asodilatation. (C) 1994 Academic Press, Inc.