Campbell William B, Falck John R
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Hypertension. 2007 Mar;49(3):590-6. doi: 10.1161/01.HYP.0000255173.50317.fc. Epub 2007 Jan 2.
The endothelium regulates vascular tone through the release of a number of soluble mediators, including NO, prostaglandin I2, and endothelium-derived hyperpolarizing factor. Epoxyeicosatrienoic acids are cytochrome P450 epoxygenase metabolites of arachidonic acid. They are synthesized by the vascular endothelium and open calcium-activated potassium channels, hyperpolarize the membrane, and relax vascular smooth muscle. Endothelium-dependent relaxations to acetylcholine, bradykinin, and shear stress that are not inhibited by cyclooxygenase and NO synthase inhibitors are mediated by the endothelium-derived hyperpolarizing factor. In arteries from experimental animals and humans, the non-NO, non-prostaglandin-mediated relaxations and endothelium-dependent hyperpolarizations are blocked by cytochrome P450 inhibitors, calcium-activated potassium channel blockers, and epoxyeicosatrienoic acid antagonists. Acetylcholine and bradykinin stimulate epoxyeicosatrienoic acid release from endothelial cells and arteries. These findings indicate that epoxyeicosatrienoic acids act as endothelium-derived hyperpolarizing factors and regulate arterial tone.
内皮细胞通过释放多种可溶性介质来调节血管张力，这些介质包括一氧化氮、前列腺素I2和内皮衍生超极化因子。环氧二十碳三烯酸是花生四烯酸的细胞色素P450环氧合酶代谢产物。它们由血管内皮合成，可打开钙激活钾通道，使细胞膜超极化，并舒张血管平滑肌。对乙酰胆碱、缓激肽和切应力的内皮依赖性舒张作用不受环氧化酶和一氧化氮合酶抑制剂的抑制，这些作用由内皮衍生超极化因子介导。在实验动物和人类的动脉中，细胞色素P450抑制剂、钙激活钾通道阻滞剂和环氧二十碳三烯酸拮抗剂可阻断非一氧化氮、非前列腺素介导的舒张作用和内皮依赖性超极化。乙酰胆碱和缓激肽可刺激内皮细胞和动脉释放环氧二十碳三烯酸。这些发现表明，环氧二十碳三烯酸作为内皮衍生超极化因子发挥作用并调节动脉张力。
