REGULATORY EFFECTS OF MYOENDOTHELIAL GAP JUNCTION ON VASCULAR REACTIVITY AFTER HEMORRHAGIC SHOCK IN RATS
REGULATORY EFFECTS OF MYOENDOTHELIAL GAP JUNCTION ON VASCULAR REACTIVITY AFTER HEMORRHAGIC SHOCK IN RATS
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DOI：
10.1097/shk.0b013e31817d3ef2-11
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发表时间：
2009-01
期刊：
影响因子：
3.1
通讯作者：
Jia Ming;Tao Li;Yuan Zhang;Jing Xu;Guangming Yang;Liangming Liu
中科院分区：
文献类型：
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作者：
Jia Ming;Tao Li;Yuan Zhang;Jing Xu;Guangming Yang;Liangming Liu
肌内皮间隙连接（Myoendothelial gap junction，MEGJ）是血管内皮细胞与血管平滑肌细胞之间的一种间隙连接，能传递电信号和化学信号，维持血管系统电活动和机械活动的同步性。在严重创伤或休克后，血管对血管收缩剂或血管扩张剂的反应性大大降低。然而，MEGJ是否参与了失血性休克后血管反应性的调节，涉及何种类型的MEGJ，以及可能的机制尚不清楚。以失血性休克大鼠及其上级肠系膜动脉（SMA）为模型，观察了破坏缝隙连接斑块的亲脂性糖苷配基18-大黄酸对去甲肾上腺素收缩血管反应的影响（内皮非依赖性血管收缩剂），杨梅素（内皮依赖性血管收缩剂）和对硝普钠的舒张反应性（内皮非依赖性血管舒张剂）和乙酰胆碱（Ach;内皮依赖性血管舒张剂）。同时，观察连接蛋白37、40和43（Cx40和Cx43）mRNA/蛋白表达与失血性休克后血管反应性变化的关系，以及Cx40或Cx43反义寡核苷酸对血管钙敏感性和血管反应性的影响。结果表明，18-甘草次酸可拮抗杨梅素和乙酰胆碱诱导的平滑肌细胞反应性，但对去甲肾上腺素和硝普钠诱导的血管反应性无影响。SMA的Cx 37和Cx40的mRNA和蛋白表达与血管反应性呈负相关，而Cx43的表达与血管反应性呈正相关。Cx40的反义寡核苷酸显著增加钙敏感性、杨梅素引起的血管收缩和乙酰胆碱引起的血管舒张，而Cx43的反义寡核苷酸则抑制它们。提示MEGJ在失血性休克后内皮依赖性血管反应性的调节中起重要作用。受累类型主要为Cx40和Cx43。Cx40/Cx43调节内皮依赖性缩血管反应性的机制可能与其调节血管平滑肌细胞的钙敏感性有关。
Myoendothelial gap junction (MEGJ), one kind of gap junction between vascular endothelial cell and vascular smooth muscle cell, can transmit electrical and chemical signals to keep the electric and machinery activity synchronism of vasculature. After severe trauma or shock, vascular reactivity to vasoconstrictors or vasodilators is greatly reduced. However, whether MEGJ participates in the regulation of vascular reactivity after hemorrhagic shock, what type of MEGJ is involved, and what is the possible mechanism are unknown. With the hemorrhagic shock Sprague-Dawley rats and their superior mesenteric arteries (SMAs), the effects of 18-glycyrrhetic acid, a lipophilic aglycone that disrupts gap junction plaques, on vascular contractile response to norepinephrine (endothelium-independent vascular constrictor), myricetin (endothelium-dependent vasoconstrictor) and relaxation reactivity to sodium nitroprusside (endothelium-independent vasodilator), and acetylcholine (Ach; endothelium-dependent vasodilator) were observed. Meanwhile, the relationship of the mRNA/protein expression of connexins 37, 40, and 43(Cx40 and Cx43) to the changes of vascular reactivity after hemorrhagic shock and the effect of antisense oligodeoxynucleotide of Cx40 or Cx43 on vascular calcium sensitivity and vascular reactivity were investigated. The results indicated that 18-glycyrrhetic acid antagonized myricetin and Ach-induced SMA reactivity, but had no effect on norepinephrine- and sodium nitroprusside-induced vascular response. The mRNA and protein expression of Cx37 and Cx40 of SMA were negatively associated with the vascular reactivity, whereas Cx43 seemed to be a positive relationship to vascular reactivity. Antisense oligodeoxynucleotide of Cx40 significantly increased the calcium sensitivity, myricetin-induced vasoconstriction, and Ach-induced vasodilation, whereas antisense oligodeoxynucleotide of Cx43 depressed them. It was suggested that MEGJ plays an important role in the regulation of endothelium-dependent vascular reactivity after hemorrhagic shock. The involved types were mainly Cx40 and Cx43. The possible mechanism that Cx40/Cx43 regulates the endothelium-dependent vasoconstrictor reactivity may be related to their regulating effects on the calcium sensitivity of vascular smooth muscle cell.