COMPARISON OF THE EFFECTS OF NITRIC-OXIDE AND PEROXYNITRITE ON THE 12-LIPOXYGENASE AND CYCLOOXYGENASE METABOLISM OF ARACHIDONIC-ACID IN RABBIT PLATELETS
Y. Fujimoto et al., COMPARISON OF THE EFFECTS OF NITRIC-OXIDE AND PEROXYNITRITE ON THE 12-LIPOXYGENASE AND CYCLOOXYGENASE METABOLISM OF ARACHIDONIC-ACID IN RABBIT PLATELETS, Prostaglandins, leukotrienes and essential fatty acids, 59(2), 1998, pp. 95-100
The effects of a new type of nitric oxide (NO)-releasing compound, oxo
-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC7), and peroxynitr
ite (ONOO-) on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic
acid (12-HETE), thromboxane (TX) B-2 and 12-hydroxy-5,8,10-heptadecatr
ienoic acid (HHT) from exogenous arachidonic acid in washed rabbit pla
telets have been compared. At concentrations of 5 mu M and below, NOC7
inhibited 12-HETE formation (56.5-98.8% inhibition). Moreover, NOC7 i
nhibited TXB2 and HHT formation at concentrations ranging from 5 to 20
mu M (TXB2, 62.2-88.1% inhibition; HHT, 11.6-62.2% inhibition). ONOO-
had little or no effect on the production of these three metabolites
at concentrations of up to 50 mu M. Experiments utilizing a new class
of NO antidote, oxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-o
xide, revealed that the observed effects of NOC7 are caused by NO. The
effects of NO were reversed by addition of the superoxide generating
system (xanthine plus xanthine oxidase and catalase), indicating that
superoxide is a vital modulator of the action of NO. These results sug
gest that NO, but not ONOO- (up to 50 mu M), can be a potent dual inhi
bitor of the 12-lipoxygenase and cyclooxygenase activities in platelet
s and that superoxide is an important regulator of the action of NO.