LY 255283

LY 255283 is a specific antagonit of leukotriene B4 (LTB4) receptor. It inhibits the production of LTB (4) in human peripheral blood polymorphonuclear leukocytes (PMNL) and in monocytes activated by calcium ionophore A23187.All seven rats given only the vehicle died within 2 h of reperfusion, whereas rats treated with LY-255283 (3 or 10 mg/kg iv), a leukotriene B4 (LTB4) receptor antagonist given 10 min before reperfusion, exhibited significantly higher survival rates of 57% (4 out of 7) and 75% (6 out of 8), respectively, 2 h after reperfusion. Rats given 1 mg/kg of LY-255283 showed no significant improvement in survival. Splanchnic artery occlusion (SAO) -shock rats treated with LY-255283 (3 or 10 mg/kg) exhibited significantly attenuated accumulation of plasma free amino-nitrogenous compounds and of a myocardial depressant factor. Treatment with LY-255283 (10 mg/kg) markedly (P less than 0.01) ameliorated the deficits of endothelium-dependent relaxation of isolated superior mesenteric artery (SMA) rings in untreated SAO-shock rats. LY-255283 at 10 mg/kg significantly attenuated the increased myeloperoxidase activity in the intestinal tissue of SAO-shock rats.