Increased endothelin-1 reactivity and endothelial dysfunction in carotid arteries from rats with hyperhomocysteinemia

Background and purpose:

There are interactions between endothelin-1 (ET-1) and endothelial vascular injury in hyperhomocysteinemia (HHcy), but the underlying mechanisms are poorly understood. Here we evaluated the effects of HHcy on the endothelin system in rat carotid arteries.

Experimental approach:

Vascular reactivity to ET-1 and ET_A and ET_B receptor antagonists was assessed in rings of carotid arteries from normal rats and those with HHcy. ET_A and ET_B receptor expression was assessed by mRNA (RT-PCR), immunohistochemistry and binding of [¹²⁵I]-ET-1.

Key results:

HHcy enhanced ET-1-induced contractions of carotid rings with intact endothelium. Selective antagonism of ET_A or ET_B receptors produced concentration-dependent rightward displacements of ET-1 concentration response curves. Antagonism of ET_A but not of ET_B receptors abolished enhancement in HHcy tissues. ET_A and ET_B receptor gene expressions were not up-regulated. ET_A receptor expression in the arterial media was higher in HHcy arteries. Contractions to big ET-1 served as indicators of endothelin-converting enzyme activity, which was decreased by HHcy, without reduction of ET-1 levels. ET-1-induced Rho-kinase activity, calcium release and influx were increased by HHcy. Pre-treatment with indomethacin reversed enhanced responses to ET-1 in HHcy tissues, which were reduced also by a thromboxane A₂ receptor antagonist. Induced relaxation was reduced by BQ788, absent in endothelium-denuded arteries and was decreased in HHcy due to reduced bioavailability of NO.

Conclusions and implications:

Increased ET_A receptor density plays a fundamental role in endothelial injury induced by HHcy. ET-1 activation of ET_A receptors in HHcy changed the balance between endothelium-derived relaxing and contracting factors, favouring enhanced contractility.British Journal of Pharmacology (2009) 157, 568–580; doi:10.1111/j.1476-5381.2009.00165.x; published online 9 April 2009This article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

新型输送型球囊扩张导管在颅内动脉狭窄治疗中的临床应用研究

目的：探讨新型输送型球囊扩张导管(Fastunnel)在颅内动脉粥样硬化狭窄介入治疗中的应用效果。方法：2021年11月至2022年2月,我们使用新型输送型球囊扩张导管对10例颅内动脉粥样硬化狭窄的患者进行了球囊扩张+支架成形术。收集并分析了患者的基线情况、影像学特点、治疗情况及围手术期情况。结果：男6例,女性4例,平均年龄(62.7±6.7)岁。10例患者均成功接受手术治疗,手术时长为16~65(37.3±18.2)min,治疗过程所受辐射剂量为1381~4901(2643.7±1131.7)mGy,剂量面积乘积(DAP)值为5707~38112(17526.8±10809.5)μGym₂^。围手术期无出血及缺血相关并发症。结论：输送型球囊扩张导管具有较好的安全性,能有效地简化手术步骤、缩短手术时间,对减少患者及医生所受射线剂量。