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再灌注对三种收缩模型中血管平滑肌反应性的影响。

Effect of reperfusion on vascular smooth muscle reactivity in three contraction models.

作者信息

Grześk Elżbieta, Darwish Nasser, Stolarek Wioleta, Wiciński Michał, Malinowski Bartosz, Burdziński Igor, Grześk Grzegorz

机构信息

Department of Pediatrics Hematology and Oncology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.

2nd Department of Cardiology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.

出版信息

Microvasc Res. 2019 Jan;121:24-29. doi: 10.1016/j.mvr.2018.09.002. Epub 2018 Sep 12.

Abstract

BACKGROUND

Ischemia and reperfusion remain inseparable elements of numerous medical procedures such as by-pass surgery, organ transplantation or other cardiology and intervention radiology. The contraction of the smooth muscle of the vessel is considered to be one of the basic components leading to impaired perfusion, an increase in the oxygen deficit of the endothelium of the vessel, and subsequently also to tissues vascularized by the vessel. Main aim of this study was to evaluate the effect of ischemia and reperfusion on vascular smooth muscle cells stimulated pharmacologically with mastoparan-7 (direct G-protein activator) in comparison to stimulation of G-protein coupled receptor agonist - phenylephrine, and direct calcium channel activator - Bay K8644.

MATERIAL AND METHODS

Experiments were performed on isolated and perfused tail artery of Wistar rats. Contraction force in our model was measured by increased level of perfusion pressure with a constant flow.

RESULTS

Concentration-response curves obtained for phenylephrine, mastoparan-7 and Bay K8644 presented a sigmoidal relation. Ischemia induced hyporreactivity of vessels, whereas during reperfusion the significant time related hyperreactivity for phenylephrine and mastoparan-7 only but not for Bay K8644. These reactions were secondary to the modulation of calcium influx from intra- and extracellular calcium stores.

CONCLUSIONS

Results of our experiments suggest that mastoparan-7 significantly induces contraction of vascular smooth muscle cells not only for controls but in the presence of ischemia and reperfusion too. Potential therapeutic applications of the observed reactions are important. They may include regenerative processes within the nervous system, studies on the improvement of blood flow within the microcirculation, or antimicrobial activity. Modulation of the G protein-phospholipase C response may also be an interesting point of action of future drugs modifying the response to stimulation during ischemia in particular, such activities could take place during the transport of organs for transplantation.

摘要

背景

缺血和再灌注仍然是众多医疗程序中不可分割的要素,如搭桥手术、器官移植或其他心脏病学及介入放射学手术。血管平滑肌的收缩被认为是导致灌注受损、血管内皮氧亏增加以及随后由该血管供血的组织氧亏增加的基本组成部分之一。本研究的主要目的是评估与刺激G蛋白偶联受体激动剂——去氧肾上腺素以及直接钙通道激活剂——Bay K8644相比,缺血和再灌注对用马斯托帕兰-7(直接G蛋白激活剂)进行药理学刺激的血管平滑肌细胞的影响。

材料与方法

实验在Wistar大鼠分离并灌注的尾动脉上进行。在我们的模型中,收缩力通过在恒定流量下灌注压力水平的升高来测量。

结果

去氧肾上腺素、马斯托帕兰-7和Bay K8644的浓度-反应曲线呈S形关系。缺血诱导血管反应性降低,而在再灌注期间,仅去氧肾上腺素和马斯托帕兰-7出现与时间相关的显著反应性增强,而Bay K8644未出现。这些反应继发于细胞内和细胞外钙库钙内流的调节。

结论

我们的实验结果表明,马斯托帕兰-7不仅在对照情况下,而且在存在缺血和再灌注的情况下,均能显著诱导血管平滑肌细胞收缩。观察到的这些反应的潜在治疗应用很重要。它们可能包括神经系统内的再生过程、微循环内血流改善的研究或抗菌活性。G蛋白-磷脂酶C反应的调节也可能是未来药物的一个有趣作用点,特别是那些改变缺血期间对刺激反应的药物,此类作用可能发生在器官移植运输过程中。

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