Exogenous, basal, and flow‐induced nitric oxide production and endothelial cell proliferation
Exogenous, basal, and flow‐induced nitric oxide production and endothelial cell proliferation
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DOI：
10.1002/(sici)1097-4652(199706)171:3
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发表时间：
1997-06
影响因子：
5.6
通讯作者：
K. Gooch;C. Dangler;J. Frangos
中科院分区：
文献类型：
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作者：
K. Gooch;C. Dangler;J. Frangos
研究了内源性和外源性一氧化氮（NO）在调节大血管和微血管内皮细胞增殖中的作用。从5种不同的化学供体中释放的外源性NO以剂量依赖性的方式抑制牛主动脉、牛视网膜微血管和人脐静脉内皮细胞的增殖。供体的效力随供体半衰期的变化而变化。半衰期大于30分钟的供体比半衰期明显较短的供体更有效。内皮细胞与0.4 mM脱氧腺苷和0.4 mM脱氧鸟苷共孵育可降低NO供体引起的抑制百分比。这些数据与依赖核糖核苷酸还原酶的抑制机制一致。四种不同的一氧化氮合酶（NOS）抑制剂对基础NO生成的抑制没有改变细胞增殖。22 dyn/cm2的层流对牛主动脉内皮细胞的增殖有抑制作用。添加NOS抑制剂并没有消除血流诱导的增殖抑制，这表明血流刺激内皮细胞释放NO并不能解释血流诱导的增殖抑制。综上所述，这些数据表明，相对高浓度的外源性NO抑制内皮细胞增殖，而内源性NO不足以抑制增殖。j .细胞。中国生物医学工程学报（英文版）。©1997 Wiley‐Liss, Inc。
The role of nitric oxide (NO) from endogenous and exogenous sources in regulating large vessel and microvascular endothelial cell proliferation was investigated. Exogenous NO liberated from five different chemical donors inhibited bovine aortic, bovine retinal microvascular, and human umbilical vein endothelial cell proliferation in a dose‐dependent manner as determined by 3H‐thymidine incorporation. The potency of the donors varied as a function of the donors' half‐lives. Donors with half‐lives greater than 30 min were more effective than donors with significantly shorter half‐lives. Coincubation of endothelial cells with 0.4 mM deoxyadenosine and 0.4 mM deoxyguanosine reduced the percentage of inhibition due to an NO donor. These data are consistent with a ribonucleotide reductase‐dependent mechanism of inhibition. Inhibition of basal NO production with four different inhibitors of nitric oxide synthase (NOS) did not modify proliferation. Laminar flow with a wall shear stress of 22 dyn/cm2inhibited the proliferation of subconfluent bovine aortic endothelial cells. The addition of a NOS inhibitor did not abrogate the flow‐induced inhibition of proliferation, suggesting that flow‐stimulated release of NO from endothelial cells did not account for flow‐induced inhibition of proliferation. Taken together, these data suggest that relatively large concentrations of exogenous NO inhibit endothelial cell proliferation, while endogenous levels of NO are inadequate to inhibit proliferation. J. Cell. Physiol. 171:252–258, 1997. © 1997 Wiley‐Liss, Inc.