Yang B C, Khan S, Mehta J L
Department of Medicine, University of Florida College of Medicine, Gainesville.
Am J Physiol. 1994 Jun;266(6 Pt 2):H2212-9. doi: 10.1152/ajpheart.1994.266.6.H2212.
Platelet-induced relaxation of endothelium-intact vascular tissues, mediated via release of endothelium-derived relaxing factor (EDRF), is diminished or lost after ischemia and reperfusion. Release of oxygen free radicals during ischemia-reperfusion may degrade EDRF and influence response of vascular tissues to platelets. To determine platelet modulation of tone of blood vessels treated with oxygen free radicals, rat aortic rings with intact endothelium were exposed to xanthine (X) plus xanthine oxidase (XO) 5 min before contraction with norepinephrine followed by exposure of rings to platelets. Treatment of aortic rings with X+XO caused a modest contraction, potentiated norepinephrine-mediated contraction, and inhibited platelet-mediated vasorelaxation. Exposure of aortic rings to X+XO also decreased ADP- as well as acetylcholine-mediated relaxation. Pretreatment of rings with superoxide dismutase or catalase did not change X+XO-induced inhibition of platelet-mediated relaxation, but it abolished the X+XO-induced contraction of rings as well as subsequent potentiation of norepinephrine-mediated contraction. Pretreatment of rings with hydroxyl radical scavengers dimethyl-2-thiourea, dimethyl sulfoxide, mannitol, or histidine attenuated the X+XO-induced inhibition of platelet-mediated relaxation, although these agents did not affect X+XO-induced contraction of rings. This study indicates that the vasoconstriction on exposure of aortic rings to X+XO is due to generation of superoxide anions, whereas inhibition of platelet-mediated relaxation after exposure of vessels to X+XO is due, at least in part, to release of hydroxyl radicals. Release of superoxide anions and hydroxyl radicals after temporary arterial occlusion may be the basis of subsequent modulation of vascular tone.
血小板诱导的内皮完整血管组织舒张是通过释放内皮源性舒张因子（EDRF）介导的，在缺血再灌注后这种舒张作用会减弱或丧失。缺血再灌注期间氧自由基的释放可能会降解EDRF并影响血管组织对血小板的反应。为了确定血小板对经氧自由基处理的血管张力的调节作用，将具有完整内皮的大鼠主动脉环在与去甲肾上腺素收缩前5分钟暴露于黄嘌呤（X）加黄嘌呤氧化酶（XO），然后将环暴露于血小板。用X + XO处理主动脉环会引起适度收缩，增强去甲肾上腺素介导的收缩，并抑制血小板介导的血管舒张。将主动脉环暴露于X + XO还会降低ADP以及乙酰胆碱介导的舒张作用。用超氧化物歧化酶或过氧化氢酶预处理环并不能改变X + XO诱导的对血小板介导舒张的抑制作用，但它消除了X + XO诱导的环收缩以及随后去甲肾上腺素介导收缩的增强。用羟自由基清除剂二甲基-2-硫脲、二甲基亚砜、甘露醇或组氨酸预处理环可减弱X + XO诱导的对血小板介导舒张的抑制作用，尽管这些试剂不影响X + XO诱导的环收缩。这项研究表明，主动脉环暴露于X + XO时的血管收缩是由于超氧阴离子的产生，而血管暴露于X + XO后血小板介导舒张的抑制至少部分是由于羟自由基的释放。短暂动脉闭塞后超氧阴离子和羟自由基的释放可能是随后血管张力调节的基础。
