Endotoxic
shock is a systemic inflammatory response that is associated with an increase in
nitric oxide production and a decrease in the formation of
20-hydroxyeicosatetraenoic acid (20-HETE), which may contribute to the fall in blood pressure and vascular reactivity. The present study examined the effects of a synthetic analogue of
20-HETE, N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]
glycine (5,14-HEDGE), on the fall in blood pressure and vascular responsiveness to vasoscontrictors and
acetylcholine in rats treated with
endotoxin. The MAP fell by 31 mmHg, and the heart rate rose by 90 beats/min in male Wistar rats treated with
endotoxin (10 mg/kg, intraperitoneally). The fall in MAP was associated with a decrease in the
vasoconstrictor response to
norepinephrine in isolated aorta and superior mesenteric artery and increased levels of
nitrite in the serum, kidney, heart, and vascular tissues. The effects of
endotoxin were prevented by
5,14-HEDGE (30 mg/kg, s.c.) given 1 h after injection of
endotoxin. Furthermore, a competitive antagonist of
vasoconstrictor effects of
20-HETE,
20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (30 mg/kg, s.c.), prevented the beneficial effects of
5,14-HEDGE on MAP and vascular tone in rats treated with
endotoxin. These data are consistent with the view that a fall in the production of
20-HETE contributes to the fall in MAP and vascular reactivity in rats treated with
endotoxin, and that
5,14-HEDGE has a beneficial effect.