Sequential release of leukotrienes and norepinephrine in rat bowel after platelet-activating factor. A mechanistic study of platelet-activating factor-induced bowel necrosis.

We have developed a model of ischemic bowel necrosis in the rat by injecting synthetic platelet-activating factor into the mesenteric vascular bed. Our previous studies have shown that the development of ischemic necrosis was not due to thrombus formation, but to release of vasoconstricting mediators from the intestinal tissue, such as leukotriene C4. However the release of leukotriene C4 was transient and could not account for the prolonged intestinal vasoconstriction. In the present study, we show that (a) the release of norepinephrine from intestinal tissue was increased after injection of platelet-activating factor, and was responsible, at least in part, for the prolonged vasoconstriction; (b) in vivo treatment with reserpine abolished both the prolonged vasoconstriction and the release of norepinephrine from the perfused small intestine; (c) the release of norepinephrine was largely secondary to leukotriene C4 production and direct injection of leukotriene C4 caused catecholamine release; and (d) there was a concomitant release of epinephrine (of a lesser magnitude) after injection of platelet-activating factor.