Recombinant gene transfer of endothelial nitric oxide synthase augments coronary artery relaxations during hypoxia.
Recombinant gene transfer of endothelial nitric oxide synthase augments coronary artery relaxations during hypoxia.
复制标题
内皮一氧化氮合酶的重组基因转移可增强缺氧期间冠状动脉的松弛。
DOI：
10.1161/01.cir.100.suppl_2.ii-335
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发表时间：
1999
期刊：
影响因子：
37.8
通讯作者：
Schaff,HV
中科院分区：
文献类型：
--
作者：
Cable,DG;Pompili,VJ;O'Brien,T;Schaff,HV
背景——冠状动脉对缺氧的反应是短暂的松弛，这在一定程度上是通过释放一氧化氮来增加冠状动脉血流量的。我们假设一氧化氮合酶表达的增加可能会进一步增强缺氧期间的血管松弛。本研究检查了腺病毒介导的牛内皮一氧化氮合酶 (eNOS) 转移对缺氧引起的犬冠状动脉短暂舒张的影响。方法和结果——将成对的冠状动脉节段暴露于载体（含白蛋白的磷酸盐缓冲盐水）或编码大肠杆菌β-半乳糖苷酶（Ad.CMVLacZ，病毒对照；1010pfu/mL）或 eNOS 的腺病毒（Ad.CMVeNOS；1010pfu/mL）37°C 2 小时。使用 eNOS 特异性单克隆抗体进行的免疫组织化学记录了 Ad.CMVeNOS 动脉中的内皮和外膜表达，而媒介物和病毒对照仅显示组成型表达。与对照组相比，Ad.CMVeNOS 动脉中的 cGMP 水平增加了 5 倍。在暴露于 Ad.CMVeNOS 的动脉中，与病毒对照相比，前列腺素 F2α 的最大收缩减少，并且通过 eNOS 竞争性抑制剂（NG-单甲基-l-精氨酸，10−3mol/L）预处理消除了这种影响。与媒介物 (26.3±6.0%) 或病毒 (27.2±7.1%) 对照相比，Ad.CMVeNOS 动脉 (45.2±8.8%，n=6) 中缺氧诱导的短暂舒张 (95% N2-5% CO2) 增强。这种增加一氧化氮产生的方法可能有利于减少冠状动脉血管痉挛。
Background—Coronary arteries respond to hypoxia with transient relaxations, which increases coronary blood flow, in part, by release of nitric oxide. We hypothesized that increased expression of nitric oxide synthase might further augment blood vessel relaxation during hypoxia. The present study examined the effect of adenovirus-mediated transfer of bovine endothelial nitric oxide synthase (eNOS) on hypoxia-induced transient relaxations in canine coronary arteries.Methods and Results—Paired segments of coronary arteries were exposed to vehicle (phosphate-buffered saline with albumin) or an adenovirus encoding eitherE coliβ-galactosidase (Ad.CMVLacZ, viral control; 1010pfu/mL) or eNOS (Ad.CMVeNOS; 1010pfu/mL) for 2 hours at 37°C. Immunohistochemistry with a monoclonal antibody specific for eNOS documented both endothelial and adventitial expression in Ad.CMVeNOS arteries, whereas vehicle and viral controls demonstrated only constitutive expression. Levels of cGMP were increased 5-fold in Ad.CMVeNOS arteries compared with controls. In arteries exposed to Ad.CMVeNOS, maximum contraction to prostaglandin F2αwas reduced compared with viral controls, and this effect was eliminated by pretreatment with a competitive inhibitor of eNOS (NG-monomethyl-l-arginine, 10−3mol/L). Hypoxia-induced transient relaxation (95% N2-5% CO2) in Ad.CMVeNOS arteries (45.2±8.8%, n=6) was augmented compared with vehicle (26.3±6.0%) or viral (27.2±7.1%) controls.Conclusions—Adenovirus-mediated gene transfer of nitric oxide synthase reduces receptor-dependent contractions and augments hypoxia-induced relaxations in canine coronary arteries; this method of augmentation of NO production might be advantageous for reduction of coronary artery vasospasm.