Increased O2•- production and upregulation of ETB receptors by sympathetic neurons in DOCA-salt hypertensive rats
Increased O2•- production and upregulation of ETB receptors by sympathetic neurons in DOCA-salt hypertensive rats
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DOI：
10.1161/01.hyp.0000126068.27125.42
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发表时间：
2004-05-01
期刊：
影响因子：
8.3
通讯作者：
Kreulen, DL
中科院分区：
文献类型：
--
作者：
Dai, XL;Galligan, JJ;Kreulen, DL
超氧阴离子（O-2（.-））在高血压动物的血管系统中，O-2的产生是升高的，但尚不清楚O-2（.-）在交感神经系统中的产生也增加。我们测量了O-2（.-）用二氢乙啶（DHE）荧光法测定醋酸去氧皮质酮（DOCA）盐高血压大鼠椎前交感神经节中的水平。O-2（.-）DOCA-盐大鼠的神经节中，与血压正常的假手术大鼠相比升高。用内皮素（ET）-1（3 × 10（-8）mol/L）处理神经节可使神经元荧光强度增加200%，而ETB受体拮抗剂BQ 788（10（-7）mol/L）可使其减弱。ET-1还可增加O2-（.-）在分离的交感神经元和PC-12细胞中通过激活ETB受体而不是ETA受体诱导荧光。为了评估神经节中ET- 1水平升高是否可能导致O-2（.-）我们使用ELISA测定法测量了在神经节中发现的ET-1的量。假手术大鼠腹腔神经节中的ET- 1水平为695.6 +/- 40.9皮克/克;它们与DOCA-盐大鼠神经节中的ET- 1水平没有差异。然后，我们比较了假手术和DOCA-盐动物神经节中的ETB受体水平。DOCA-盐组大鼠腹腔神经节ETB受体mRNA水平和ETB受体蛋白水平分别比假手术组大鼠高32%和20%。总之，O-2（.-）DOCA盐性高血压时椎前交感神经节中ET-1升高，ET- 1是升高O-2（.-）交感神经节中的水平，这可能是由ETB受体的上调介导的作用。
Superoxide anion (O-2(.-)) production is elevated in the vasculature of hypertensive animals but it is not known if O-2(.-) production is also elevated in the sympathetic nervous system. We measured O-2(.-) levels in prevertebral sympathetic ganglia of deoxycorticosterone acetate (DOCA)-salt hypertensive rats using the dihydroethidine (DHE) fluorescence method. O-2(.-) was elevated in ganglia from DOCA-salt rats compared with normotensive sham rats. Treatment of ganglia with endothelin (ET)-1 ( 3 x 10(-8) mol/L) resulted in a 200% increase in fluorescence intensity in neurons, which was attenuated by the ETB receptor antagonist BQ788 (10(-7) mol/L). ET-1 also increased the O-2(.-) induced fluorescence in dissociated sympathetic neurons and PC-12 cells via activation of ETB receptors, but not ETA receptors. To evaluate whether elevated ET- 1 levels in the ganglia might contribute to the elevated O-2(.-) found in ganglia we measured the amount of ET-1 using an ELISA assay. ET- 1 levels in sham rat celiac ganglia were 695.6 +/- 40.9 picogram per gram; they were not different than ET- 1 levels in ganglia from DOCA-salt rats. We then compared ETB receptor levels in ganglia from sham and DOCA-salt animals. ETB receptor mRNA levels were 32% higher and ETB receptor protein levels were 20% higher in celiac ganglia from DOCA-salt rats than from sham rats separately. In conclusion, O-2(.-) is elevated in prevertebral sympathetic ganglia in DOCA-salt hypertension, and ET- 1 is a potent stimulus for the elevation of O-2(.-) levels in sympathetic ganglia, an effect that may be mediated by the upregulation of ETB receptors.