Differential regulation of NADPH oxidase in sympathetic and sensory ganglia in deoxycorticosterone acetate-salt hypertension
Differential regulation of NADPH oxidase in sympathetic and sensory ganglia in deoxycorticosterone acetate-salt hypertension
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DOI：
10.1161/hypertensionaha.107.089748
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发表时间：
2007-10-01
期刊：
影响因子：
8.3
通讯作者：
Kreulen, David L.
中科院分区：
文献类型：
--
作者：
Cao, Xian;Dai, Xiaoling;Kreulen, David L.
我们最近证实，乙酰脱氧皮质酮盐高血压大鼠椎前交感神经节超氧阴离子水平升高，这种超氧阴离子是由还原的烟酰胺腺嘌呤二核苷酸磷酸氧化酶产生的。本研究比较了背根神经节（DRG）和乳糜泻交感神经节（CG）的还原性烟酰胺-腺嘌呤二核苷酸磷酸氧化酶系统及其在高血压中的调节作用。采用二氢乙胺荧光光谱法测定神经节提取物的还原性烟酰胺-腺嘌呤二核苷酸磷酸氧化酶活性；高血压患者的背根神经节活动比正常DRG组低34%。相比之下，高血压CG的活动性比正常CG高79%。氧化酶亚基NOX1、NOX2、NOX4、p47phox和p22phox的mRNA在CG和DRG中均存在；NOX4 mRNA在CG中的表达明显高于DRG。在正常和高血压大鼠的CG和DRG中，测定膜结合催化亚基p22phox、调节亚基p47phox和Rac-1的mRNA和蛋白表达水平。p22phox mRNA和蛋白在高血压大鼠CG中表达较高，在DRG中表达较低。与正常对照组相比，高血压DRG组p47phox mRNA、蛋白及Rac-1蛋白均显著降低，而CG组无明显差异。免疫组化染色显示p47phox在高血压CG中从细胞质转移到细胞膜，而在高血压DRG中没有。这表明高血压患者交感神经元和感觉神经元中烟酰胺腺嘌呤二核苷酸磷酸氧化酶活性的减少受到相反方向的调节。这种差异调节可能导致内脏循环中血管舒缩控制不平衡和血管收缩增强。
We demonstrated recently that superoxide anion levels are elevated in prevertebral sympathetic ganglia of deoxycorticosterone acetate-salt hypertensive rats and that this superoxide anion is generated by reduced nicotinamideadenine dinucleotide phosphate oxidase. In this study we compared the reduced nicotinamide-adenine dinucleotide phosphate oxidase enzyme system of dorsal root ganglion (DRG) and sympathetic celiac ganglion (CG) and its regulation in hypertension. The reduced nicotinamide-adenine dinucleotide phosphate oxidase activity of ganglion extracts was measured using fluorescence spectrometry of dihydroethidine; the activity in hypertensive dorsal root ganglion was 34% lower than in normotensive DRG. In contrast, activity was 79% higher in hypertensive CG than normotensive CG. mRNA for the oxidase subunits NOX1, NOX2, NOX4, p47phox, and p22phox were present in both CG and DRG; mRNA for NOX4 was significantly higher in CG than in DRG. The levels of mRNA and protein expression of the membrane-bound catalytic subunit p22phox and of the regulatory subunits p47phox and Rac-1 were measured in CG and DRG in normotensive and hypertensive rats. p22phox mRNA and protein expression was greater in CG of hypertensive rats but not in DRG. Compared with normotensive controls, p47phox mRNA and protein, as well as Rac-1 protein, were significantly decreased in hypertensive DRG but not in CG. Immunohistochemical staining of p47phox showed translocation from cytoplasm to membrane in hypertensive CG but not in hypertensive DRG. This suggests that reduced nicotinamide- adenine dinucleotide phosphate oxidase activation in sympathetic neurons and sensory neurons is regulated in opposite directions in hypertension. This differential regulation may contribute to unbalanced vasomotor control and enhanced vasoconstriction in the splanchnic circulation.