RELEASE OF INTACT ENDOTHELIUM-DERIVED RELAXING FACTOR DEPENDS ON ENDOTHELIAL SUPEROXIDE-DISMUTASE ACTIVITY
RELEASE OF INTACT ENDOTHELIUM-DERIVED RELAXING FACTOR DEPENDS ON ENDOTHELIAL SUPEROXIDE-DISMUTASE ACTIVITY
复制标题
DOI：
10.1152/ajpcell.1991.260.2.c219
复制
发表时间：
1991-02-01
影响因子：
--
通讯作者：
HARRISON, DG
中科院分区：
文献类型：
--
作者：
MUGGE, A;ELWELL, JH;HARRISON, DG
内皮源性舒张因子（EDRF）被自由基迅速灭活。 内皮细胞具有多种抗氧化防御机制。 目前尚不清楚哪些内在抗氧化防御系统对保持生物活性EDRF的释放是重要的。 我们通过用3-氨基-1，2，4-三唑（AT）抑制过氧化氢酶活性，用二乙基二硫代氨基甲酸酯（DETC）抑制超氧化物歧化酶活性，以及通过用L-丁硫基-（S，R）-亚砜亚胺（BSO）抑制谷胱甘肽合成来降低谷胱甘肽含量，从而损害正常血管组织的抗氧化防御。 预处理兔主动脉在体外与DETC显着降低内皮依赖性舒张反应乙酰胆碱和钙离子载体A23187，并在较小程度上，减少内皮非依赖性舒张反应硝普钠。 用DETC预处理培养的牛主动脉内皮细胞（BAEC）并没有改变氮氧化物的释放（化学发光法测定），但预处理细胞的流出物显示出显着的抑制血管扩张活性（生物测定法测定）。 AT预处理兔离体主动脉不改变内皮依赖性和非依赖性舒张。 用BSO预处理BAEC不改变氮氧化物的释放或血管舒张活性。 这些结果表明，内皮超氧化物歧化酶的活性，而不是过氧化氢酶或谷胱甘肽，是必要的生物活性EDRF的释放。 因此，内源性超氧化物歧化酶和超氧阴离子产生的不平衡可能会导致内皮依赖性舒张功能受损，并改变血管反应性。
Endothelium-derived relaxing factor (EDRF) is rapidly inactivated by radicals. Endothelial cells possess several antioxidant defense mechanisms. It is not clear which intrinsic antioxidant defense systems are important to preserve the release of biologically active EDRF. We impaired antioxidant defense in normal vascular tissue by inhibiting catalase activity with 3-amino-1,2,4-triazole (AT), superoxide dismutase with diethyldithiocarbamate (DETC), and by reducing glutathione content via inhibiting glutathione synthesis with L-buthionine-(S,R)-sulfoximine (BSO). Pretreatment of rabbit aorta in vitro with DETC markedly reduced endothelium-dependent relaxation in response to acetylcholine and calcium ionophore A23187 and, to a lesser extent, reduced endothelium-independent relaxation in response to nitroprusside. Pretreatment of cultured bovine aortic endothelial cells (BAEC) with DETC did not alter release of nitrogen oxides (measured by chemiluminescence), but, the effluent of pretreated cells showed marked depression in vasodilator activity (measured by bioassay). Pretreatment of rabbit aorta in vitro with AT did not alter endothelium-dependent and -independent relaxations. Pretreatment of BAEC with BSO did not alter the release of nitrogen oxides or the vasodilator activity. These results suggest that endothelial superoxide dismutase activity, but not catalase or glutathione, is necessary for the release of biologically active EDRF. An imbalance of the intrinsic superoxide dismutase and the production of superoxide anions may therefore predispose to impaired endothelium-dependent relaxations and alter vascular reactivity.