Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin.
Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin.
复制标题
具有再生内皮的猪冠状动脉对聚集血小板和血清素的内皮依赖性反应性降低。
DOI：
10.1161/01.res.61.2.256
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发表时间：
1987
影响因子：
20.1
通讯作者：
Vanhoutte,PM
中科院分区：
文献类型：
--
作者：
Shimokawa,H;Aarhus,LL;Vanhoutte,PM
为了测试再生的内皮细胞引起内皮依赖性松弛的能力，对雄性约克夏猪进行了冠状动脉左前降支近端的球囊内皮剥离。血管内皮依赖性反应是在体外，取自冠状动脉裸露区域或左回旋支近端的冠脉节段环中检测的。实验在剥脱后8天或4周进行。剥脱后8天的组织学检查和对缓激肽的内皮依赖性松弛的存在证实了内皮细胞的再生；当时聚集的血小板引起了正常的内皮依赖性反应。然而，剥脱后4周，尽管有连续的内皮衬里，但对聚集血小板的松弛明显抑制，对缓激肽、二磷酸腺苷、钙离子载体A23187、血小板激活因子和凝血酶的内皮依赖性反应没有改变。剥离4周后，内皮依赖性5-羟色胺的松弛功能受到抑制。高浓度5-羟色胺可引起静止环的内皮依赖性收缩，提示再生内皮细胞在单胺作用下可能产生内皮源性收缩因子(S)，释放较少的内皮源性松弛因子(S)。5-羟色胺能拮抗剂酮丝林不能减弱血管内皮依赖性5-羟色胺的松弛作用，但联合使用5-羟色胺能阻断剂甲硫西平可阻断5-羟色胺的内皮依赖性舒张。在对照的左回旋支冠状动脉中，5-羟色胺和腺嘌呤核苷酸的释放引起了血小板的松弛，而在有内皮再生的左前降支中，这种松弛仅是由于后者。血小板引起的收缩是由于平滑肌细胞上受体的激活所致。剥离4周后，再生内皮细胞形态与天然细胞不同，呈长条形、立方形，细胞数量增加一倍。在这种状态下，先前剥离的部分出现偏心性的肌内膜增厚。这些实验表明，在慢性再生状态下，内皮细胞对聚集的血小板引起的血管收缩的保护作用受到抑制。对5-羟色胺缺乏反应性似乎是内皮功能障碍的原因。
To test the ability of regenerated endothelium to evoke endothelium-dependent relaxations, male Yorkshire pigs underwent balloon endothelial denudation of the proximal left anterior descending coronary artery. Endothelium-dependent responses were examined in vitro, in rings of coronary segments taken from the denuded area or from the proximal left circumflex coronary artery. The experiments were performed 8 days or 4 weeks after the denudation. Endothelial regrowth was confirmed by histologic examination 8 days after the denudation and by demonstrating the presence of endothelium-dependent relaxations to bradykinin; at that time aggregating platelets evoked normal endothelium-dependent responses. However, 4 weeks after the denudation, the relaxations to aggregating platelets were markedly depressed although continuous endothelial lining was present, and the endothelium-dependent responses to bradykinin, adenosine diphosphate, the Ca2+-ionophore A23187, platelet activating factor, and thrombin were unaltered. Four weeks after denudation, endothelium-dependent relaxations to serotonin were depressed. Higher concentration of serotonin induced endothelium-dependent contractions in quiescent rings with regenerated endothelium, suggesting that regenerated endothelial cells may produce endothelium-derived constricting factor(s) and release less endothelium-derived relaxing factor(s) when exposed to the monoamine. The endothelium-dependent relaxation to serotonin was not reduced by the S2-serotonergic antagonist ketanserin but prevented by the combined S1- and S2-serotonergic blocker methiothepin. The platelet-induced relaxation was due to released serotonin and adenine nucleotides in control left circumflex coronary arteries, but in left anterior descending coronary artery with regenerated endothelium, it was due solely to the latter. The platelet-induced contractions were due to activation of receptors on the smooth muscle cells. Four weeks after denudation, regenerated endothelial cells were morphologically different from native cells; they were elongated and cuboidal, and the number of the cells had increased twofold. At this state, eccentric myointimal thickening was present in the previously denuded portion. These experiments indicate that the protective role of endothelial cells against the vasoconstriction induced by aggregating platelets is depressed in the chronic regenerated state. A lack of responsiveness to serotonin appears to be the cause for the endothelial dysfunction.