Escoubet B, Griffaton G, Lechat P
Biochem Pharmacol. 1986 Jun 1;35(11):1879-82. doi: 10.1016/0006-2952(86)90306-0.
Lipoxygenase metabolites of arachidonic acid are potent chemotactic and vasoconstrictive agents and their local production in the myocardium induces the migration of polymorphonuclear cells into ischemic myocardium. These cells have been shown to play a role in the development of ischemic myocardial lesions. In the present study, the synthesis of arachidonic acid lipoxygenase metabolites by rat cardiac cells in culture and the effect of verapamil were investigated under normal and hypoxic conditions. Myocytes and fibroblasts metabolized exogenous arachidonic acid into 12-HETE and an unidentified metabolite (X). Fibroblasts synthesized significantly greater amounts of 12-HETE than myocytes (P less than 0.01). Hypoxia (glucose-free medium and low PO2) and verapamil (10(-7) M) under normal conditions, did not change metabolite synthesis by either type of cells. Under hypoxia, verapamil decreased significantly 12-HETE and X production by fibroblasts (P less than 0.01 and P less than 0.05), whereas the synthesis in myocytes was not changed. It is concluded that the decrease in lipoxygenase product synthesis under hypoxia by verapamil may contribute to its therapeutic effects on the ischemic heart.
花生四烯酸的脂氧合酶代谢产物是强效的趋化剂和血管收缩剂，它们在心肌中的局部产生会诱导多形核细胞迁移至缺血心肌。这些细胞已被证明在缺血性心肌损伤的发展中起作用。在本研究中，在正常和缺氧条件下，研究了培养的大鼠心脏细胞中花生四烯酸脂氧合酶代谢产物的合成以及维拉帕米的作用。心肌细胞和成纤维细胞将外源性花生四烯酸代谢为12-羟基二十碳四烯酸（12-HETE）和一种未鉴定的代谢产物（X）。成纤维细胞合成的12-HETE量明显多于心肌细胞（P<0.01）。正常条件下的缺氧（无糖培养基和低氧分压）和维拉帕米（10^(-7)M）均未改变两种类型细胞的代谢产物合成。在缺氧条件下，维拉帕米显著降低了成纤维细胞中12-HETE和X的产生（P<0.01和P<0.05），而心肌细胞中的合成未改变。得出的结论是，缺氧条件下维拉帕米降低脂氧合酶产物合成可能有助于其对缺血心脏的治疗作用。
