Leukotriene (LT)B4 promotes leukocyte chemotaxis and adhesion to the endothelium of postcapillary venules. The cysteinyl
leukotrienes,
LTC4,
LTD4, and
LTE4, elicit macromolecular leakage from this vessel segment. Both leukocyte adhesion to the endothelium and macromolecular leakage from postcapillary venules hallmark the microcirculatory failure after
ischemia-reperfusion, suggesting a role of
leukotrienes as mediators of
ischemia-reperfusion injury. Using the dorsal skinfold chamber model for intravital fluorescence microscopy of the microcirculation in striated muscle in awake hamsters and sequential RP-HPLC and RIA for
leukotrienes, we demonstrate in this study that (a) the
leukotrienes (LT)B4 and
LTD4 elicit leukocyte/endothelium interaction and macromolecular leakage from postcapillary venules, respectively, that (b)
leukotrienes accumulate in the tissue after
ischemia and reperfusion, and that (c) selective inhibition of
leukotriene biosynthesis (by MK-886) prevents both postischemic
leukotriene accumulation and the microcirculatory changes after
ischemia-reperfusion, while blocking of
LTD4/E4 receptors (by MK-571) inhibits postischemic macromolecular leakage. These results demonstrate a key role of
leukotrienes in
ischemia-reperfusion injury in striated muscle in vivo.