Endothelium-dependent relaxation is independent of arachidonic acid release

Endothelium-dependent relaxation is mediated by the release from vascular endothelium of an endothelium-drived relaxing factor (EDRF). It is not clear what role arachidonic acid has in this process. Inhibition of phospholipase A₂, and diacylglycerol lipase in cultured bovine aortic endothelial cells caused a marked reduction in agonist-induced arachidonic acid release from membrane phospholipid pools, and complete inhibition of prostacyclin production. EDRF release, assayed by measuring endothelium-dependent cGMP changes in mixed endothelial-smooth muscle cell cultures, was not inhibited under this conditions. In fact, EDRF release in response to two agonists, melittin and ATP, was actually increased in cells treated with phospholipase A₂ inhibitors. In addition, pretreatment of rats with high-dose dexamethasone, an inhibitor of PLA₂, did not attenuate endothelium-dependent relaxation in intact aortic rings removed from the animals, or depressor responses in anesthetized animals induced by endothelium-dependent vasodilators. In summary, inhibition of arachidonic acid release from membrane phospholipid pools does not attenuate endothelium-dependent relaxation in rats, or the release and/or response to EDRF in cultured cells.