Investigation of the vascular actions of arachidonate lipoxygenase and cyclo-oxygenase products on the isolated perfused stomach of rat and rabbit

The vascular actions of several prostanoids and arachidonate Lipoxygenase products were investigated on the gastric circulation of rat and rabbit in vitro perfused with Krebs' solution. Under resting conditions, prostacyclin and PGE2 produced small decreases in perfusion pressure with prostacyclin being the more potent. During vasoconstriction induced by infusion of noradrenaline, vasopressin or angiotensin II, prostacyclin was 20-40 times as active as PGE2 as a gastric vasodilator in rat or rabbit stomach. PGF2 alpha was a less potent vasoconstrictor than noradrenaline, while the epoxy-methano endoperoxide analogue produced a long-lasting vasoconstriction. The putative metabolite, 6-oxo-PGE1 was less active than prostacyclin as a vasodilator, having comparable activity to PGE1, whereas 6-oxo-PGF1 alpha had very little activity. The endoperoxide, PGH2 reduced perfusion pressure, this effect being inhibited by concurrent infusion of 15-HPETE. The vasodilation induced by arachidonic acid was likewise reduced by 15-HPETE, and abolished by indomethacin infusion. The arachidonate Lipoxygenase hydroperoxides were vasodilator in the gastric circulation, the rank order of potency being 12-HPETE greater than 11-HPETE greater than 5-HPETE greater than 15-HPETE in both rat and rabbit stomach. It is possible that such vasoactive Lipoxygenase products, may play modulator roles in the gastric mucosa.