Since the infusion of P-1,P-4-diadenosine 5' tetraphosphate (Ap4A) int
o animal models induces vasodilation [1,2], the present study was perf
ormed to determine whether Ap4A induces the release of nitric oxide (N
O) from endothelial cells. Ap4A induced NO release was 4.2-fold greate
r than the amount of NO released under basal condition. Ap4A induced N
O release was inhibited by N-G-nitro-L-arginine (L-NNA) and this inhib
ition was reversed by L-Arg. In addition, EGTA inhibits Ap4A induced N
O release. These data are consistent with Ap4A inducing the release of
NO from endothelial cells through the activation of endothelial nitri
c oxide synthase. (C) 1998 Federation of European Biochemical Societie
s.