Cigarette smoke-induced endothelium dysfunction: role of superoxide anion
Cigarette smoke-induced endothelium dysfunction: role of superoxide anion
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DOI：
10.1097/00004872-200105000-00009
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发表时间：
2001-05-01
影响因子：
4.9
通讯作者：
Jaimes, EA
中科院分区：
文献类型：
--
作者：
Raij, L;DeMaster, EG;Jaimes, EA
目的吸烟与冠状动脉疾病和动脉粥样硬化密切相关，吸烟可损害内皮依赖性血管舒张功能，但其机制尚不完全清楚。我们研究了超氧阴离子和收缩血管的前列腺素类在吸烟诱导的内皮功能障碍中的作用。方法在大鼠主动脉环暴露于香烟烟雾处理的Krebs缓冲液中，通过测量激动剂刺激的内皮依赖性血管舒张，用超氧化物歧化酶（SOD）以及伊非曲班、血栓素A（2）/前列腺素内过氧化物H-2（TXA（2）/PGH（2））受体阻断剂和吲哚美辛治疗（环氧合酶抑制剂）来研究超氧阴离子和缩血管类花生酸在香烟烟雾诱导的内皮功能障碍中的作用，通过在大鼠睾丸和添加eNOS辅因子的大鼠内皮细胞匀浆中将L-精氨酸转化为L-瓜氨酸来测定香烟烟雾对内皮型一氧化氮合酶（eNOS）催化活性的影响。A23187（Ca 2+离子载体）被香烟烟雾显著损害。香烟烟雾没有损害硝普钠的松弛，表明保留鸟苷酸环化酶活性。此外，香烟烟雾不影响来自先前暴露于香烟烟雾处理的Krebs缓冲液的内皮细胞或动脉瘤的匀浆中的eNOS催化活性。用SOD或伊非曲班处理以及在较小程度上用吲哚美辛处理防止了香烟烟雾诱导的内皮功能障碍。我们的研究结果表明，吸烟导致血管超氧化物生成增加，导致一氧化氮（NO）减少，生物活性并伴随增加环氧合酶依赖性和非依赖性血管收缩类花生酸的产生。J Hypertens 19：891-897（C）2001 Lippincott威廉姆斯和威尔金斯。
Objectives Cigarette smoking is strongly associated with coronary artery disease and atherosclerosis, While smoking has been shown to impair endothelium-dependent vasorelaxation, the mechanisms involved are not completely understood, We investigated the role of superoxide anion and vasoconstricting prostanoids in cigarette smoke induced endothelial dysfunction.Methods Endothelial function was assessed in rat aortic rings exposed to cigarette smoke-treated Krebs buffer, by measuring agonist stimulated endothelium-dependent vasorelaxation, Treatment with superoxide dismutase (SOD) as well as ifetroban, thromboxane A(2)/prostaglandin endoperoxide H-2 (TXA(2)/PGH(2)) receptor blocker and indomethacin (cyclooxygenase inhibitor) was used to investigate the role of superoxide anion and vasoconstricting eicosanoids on cigarette smoke-induced endothelial dysfunction, The effect of cigarette smoke on endothelial nitric oxide synthase (eNOS) catalytic activity was measured by conversion of L-arginine to L-citrulline in rat aortas and rat endothelial cell homogenates supplemented with eNOS cofactors.Results Relaxations to receptor-dependent agonists, acetylcholine and adenosine diphosphate (ADP), as well as to a receptor-independent agonist, A23187 (Ca2+ ionophore) were significantly impaired by cigarette smoke. Cigarette smoke did not impair relaxations to sodium nitroprusside, indicating preserved guanylate cyclase activity. Further, cigarette smoke did not affect eNOS catalytic activity in homogenates from either endothelial cells or aortas previously exposed to cigarette-smoke-treated Krebs buffer, Treatment with SOD or ifetroban and in a lesser degree by indomethacin prevented cigarette-smoke-induced endothelial dysfunction.Conclusions Taken together, our results suggest that cigarette smoking causes an increase in vascular superoxide production which results in decreased nitric oxide (NO) bioactivity and concomitantly increases production of cyclooxygenase dependent and independent vasoconstricting eicosanoids. J Hypertens 19:891-897 (C) 2001 Lippincott Williams & Wilkins.