Srivastava P, Hegde L G, Patnaik G K, Dikshit M
Division of Pharmacology, Central Drug Research Institute, Lucknow, PO Box 173, India.
Pharmacol Res. 1998 Oct;38(4):265-74. doi: 10.1006/phrs.1998.0357.
In the present investigation involvement of endothelial-derived reactive oxygen species (ROS) and their interaction with nitric oxide (NO), during norepinephrine (NE)-induced contraction of rat aortic rings was studied. NE (1x10(-10) M to 1x10(-5) M) caused concentration-dependent contractio n of the endothelium intact aortic rings. In the presence of hydroxyl radical scavengers, histidine (1x10(-3) M), mannitol (3x10(-3) M), dimethyl sulfoxide (50x10(-3) M) or thiourea (1x10(-3) m), superoxide dismutase (superoxide radical scavenger, SOD 10 or 100 U ml-1) or catalase (hydrogen peroxide inactivator 3, 10, or 100 U ml-1) the concentration-response curve of NE was shifted towards the right. Interestingly, in NG-nitro-l-arginine methyl ester (L-NAME) (1x10(-5) M, a NO synthase inhibitor) pretreated rings, NE-induced contractions were not inhibited by SOD or extracellular hydroxyl radical scavengers (mannitol and histidine). However, in these rings NE-induced contractions were found to be attenuated by endogenous hydroxyl radical scavengers (thiourea and DMSO) or catalase. In the endothelium denuded rings no significant effect of these scavengers on NE-induced contractions was observed. These results thus indicate the involvement of endothelium-derived hydrogen peroxide, superoxide and hydroxyl radicals in the NE-induced contractions. In addition, endothelial NO interacts with the ROS generated during rat aortic ring contractions.
在本研究中，我们探究了内皮源性活性氧（ROS）的参与情况以及它们在去甲肾上腺素（NE）诱导大鼠主动脉环收缩过程中与一氧化氮（NO）的相互作用。NE（1×10⁻¹⁰ M至1×10⁻⁵ M）引起内皮完整的主动脉环浓度依赖性收缩。在存在羟基自由基清除剂（组氨酸，1×10⁻³ M；甘露醇，3×10⁻³ M；二甲基亚砜，50×10⁻³ M或硫脲，1×10⁻³ m）、超氧化物歧化酶（超氧阴离子自由基清除剂，SOD 10或100 U/ml⁻¹）或过氧化氢酶（过氧化氢灭活剂3、10或100 U/ml⁻¹）的情况下，NE的浓度 - 反应曲线向右移动。有趣的是，在经NG - 硝基 - l - 精氨酸甲酯（L - NAME，1×10⁻⁵ M，一种NO合酶抑制剂）预处理的血管环中，NE诱导的收缩不受SOD或细胞外羟基自由基清除剂（甘露醇和组氨酸）的抑制。然而，在这些血管环中，NE诱导的收缩被内源性羟基自由基清除剂（硫脲和二甲基亚砜）或过氧化氢酶减弱。在去内皮的血管环中，未观察到这些清除剂对NE诱导收缩的显著影响。因此，这些结果表明内皮源性过氧化氢、超氧化物和羟基自由基参与了NE诱导的收缩。此外，内皮NO与大鼠主动脉环收缩过程中产生的ROS相互作用。
