METABOLISM OF ARACHIDONIC-ACID BY CANINE POLYMORPHONUCLEAR LEUKOCYTESSYNTHESIS OF LIPOXYGENASE AND OMEGA-OXIDIZED METABOLITES

Both polymorphonuclear (PMN) leukocytes and metabolites of arachidonic acid, especially lipoxygenase products, have been reported to contrib ute to myocardial damage after coronary artery occlusion and reperfusi on. While canine models of myocardial ischemia were used in many of th ese studies, very little is known about arachidonic acid metabolism by canine PMNs. Moreover, it is unclear whether arachidonic acid metabol ites released by canine PMNs affect vascular tone. Therefore, we chara cterized arachidonic acid metabolism by canine PMNs and determined the effect of these metabolites on vascular tone of isolated canine coron ary arteries. Suspensions of canine PMNs were incubated with [C-14]ara chidonic acid and the calcium ionophore A23187. The incubation media w as extracted, and the metabolites resolved by HPLC. 20-Hydroxy-leukotr iene B-4 (LTB(4)), 12,20-dihydroxyeicosatetraenoic acid (diHETE), LTB( 4), 12-hydroxyheptadeclatrienoic acid (HHT), and 12-(S)-hydroxyeicosat etraenoic acid (HETE) were isolated, and their structures confirmed by gas chromatography/mass spectrometry. There was also evidence for the formation of 20-HETE, thromboxane B-2 (TXB(2)), 5-HETE, and several i somers of LTB(4). None of the arachidonic acid metabolites that were i solated from incubates of canine PMNs augmented vascular tone, but mat erial migrating with 12,20-diHETE relaxed canine coronary arteries. Au thentic 12(S),20-diHETE also produced a concentration-related relaxati on of canine coronary artery. 12(R), 20-diHETE was inactive. 20-HETE i nhibited A23187-induced PMN aggregation. Thus, arachidonic acid is met abolized in canine PMNs through the cyclooxygenase, lipoxygenases and cytochrome P-450 pathways. Whether these metabolites contribute to myo cardial injury remains to be determined.