Evidence that expression of inducible nitric oxide synthase in response to endotoxin is augmented in atherosclerotic rabbits.
Evidence that expression of inducible nitric oxide synthase in response to endotoxin is augmented in atherosclerotic rabbits.
复制标题
有证据表明，动脉粥样硬化兔中响应内毒素的诱导型一氧化氮合酶的表达增强。
DOI：
10.1161/01.res.77.3.536
复制
发表时间：
1995
影响因子：
20.1
通讯作者：
Heistad,DD
中科院分区：
文献类型：
--
作者：
Sobey,CG;Brooks2nd,RM;Heistad,DD
动脉粥样硬化病变含有单核细胞/巨噬细胞和血管平滑肌细胞，因此可能通过诱导型一氧化氮合酶（NOS）产生一氧化氮的能力增加。我们使用三种方法（收缩反应、从 1-精氨酸生成 1-瓜氨酸以及用 NADPH 心肌黄酶染色）来检验以下假设：在体内施用脂多糖 (LPS) 后，动脉粥样硬化动脉中诱导型 NOS 产生的一氧化氮增加。将新西兰白兔（正常，n = 18）和渡边遗传性高脂血症（动脉粥样硬化，n = 21）兔麻醉并静脉注射载体或LPS。体内注射LPS 4小时后，在体外检查主动脉节段的收缩反应性。经过 LPS 处理的动脉粥样硬化兔子的主动脉收缩敏感性大幅下降（约五倍），而正常兔子的主动脉收缩敏感性小幅下降（约两倍）。主动脉节段与抑制诱导型 NOS 的氨基胍一起孵育，可在 LPS 治疗后恢复收缩反应。主动脉段将[14C]1-精氨酸转化为[14C]1-瓜氨酸的体外测定表明，经过LPS处理的动脉粥样硬化主动脉，[14C]1-精氨酸的钙依赖性转化显着增加（约五倍），但正常主动脉则不然。 NADPH-心肌黄酶染色显示，仅在正常兔子的内皮细胞以及媒介物和LPS处理的兔子的动脉粥样硬化主动脉的病变和中层中出现阳性细胞。这些 NADPH 心肌黄酶阳性细胞的总体分布类似于平滑肌细胞，而不是巨噬细胞。因此，收缩反应的损害、1-瓜氨酸的产生以及NADPH-心肌黄酶染色表明动脉粥样硬化动脉通过诱导型NOS产生一氧化氮的能力增加。
Atherosclerotic lesions contain monocytes/macrophages and vascular smooth muscle cells and thus may have an increased capacity for generation of nitric oxide by inducible nitric oxide synthase (NOS). We used three approaches (contractile responses, generation ofl-citrulline froml-arginine, and staining with NADPH-diaphorase) to test the hypothesis that after administration of lipopolysaccharide (LPS) in vivo, generation of nitric oxide by inducible NOS is augmented in atherosclerotic arteries. New Zealand White (normal, n=18) and Watanabe heritable hyperlipidemic (atherosclerotic, n=21) rabbits were anesthetized and injected intravenously with vehicle or LPS. Contractile responsiveness of aortic segments was examined in vitro 4 hours after injection of LPS in vivo. There was a substantial (approximately fivefold) decrease in contractile sensitivity of aortas from LPS-treated atherosclerotic rabbits and a small (approximately twofold) decrease in normal rabbits. Incubation of aortic segments with aminoguanidine, which inhibits inducible NOS, restored contractile responsiveness after LPS treatment. In vitro assay of conversion of [14C]l-arginine to [14C]l-citrulline by aortic segments demonstrated marked (approximately fivefold) increase in calcium-independent conversion of [14C]l-arginine by LPS-treated atherosclerotic, but not normal, aortas. NADPH-diaphorase staining demonstrated positive cells only in the endothelium of normal rabbits and in the lesions and media of the atherosclerotic aortas in both vehicle- and LPS-treated rabbits. The general distribution of these NADPH-diaphorase–positive cells resembled that of smooth muscle cells and not macrophages. Thus, impairment of contractile responses, generation ofl-citrulline, and staining with NADPH-diaphorase suggest that atherosclerotic arteries have increased capacity for generation of nitric oxide by inducible NOS.