Elevated K+ channel activity opposes vasoconstrictor response to serotonin in cerebral arteries of the Fawn Hooded Hypertensive rat.
Elevated K+ channel activity opposes vasoconstrictor response to serotonin in cerebral arteries of the Fawn Hooded Hypertensive rat.
复制标题
DOI：
10.1152/physiolgenomics.00072.2016
复制
发表时间：
2017-01-01
影响因子：
4.6
通讯作者：
Roman RJ
中科院分区：
文献类型：
--
作者：
Pabbidi MR;Roman RJ
先前的研究表明，小鹿帽状高血压（FHH）大鼠的大脑中动脉（MCAs）表现出肌原性反应受损，而含有15个基因的Brown Norway染色体1小区域的渗入恢复了FHH. 10基因大鼠的肌原性反应。FHH大鼠的肌生成反应受损与血管平滑肌细胞（VSMCs）中大电导钾（BK）通道活性增加有关。本研究探讨了FHH大鼠BK通道功能的增加是否会改变血管收缩剂对5-羟色胺（5-HT）的反应。与FHH. 10 - 1大鼠相比，FHH的基底肌张力和自发性肌生成反应分别减弱约2倍和5倍。与FHH. 10大鼠相比，5-HT （0.1 μM）介导的血管收缩降低了约2倍，抑制BK通道使FHH的血管收缩反应增加了约3倍。5-HT （3 μM）降低了FHH. 10 - 1分离的VSMCs的BK通道和自发瞬时外向电流，但对FHH大鼠无影响。与FHH大鼠相比，5-HT对FHH. 10大鼠MCAs膜电位的去极化作用显著。阻断BK通道正常化5- ht诱导的FHH大鼠MCAs去极化。与FHH. 10亿大鼠相比，FHH VSMCs平台期5- ht介导的胞质钙浓度升高明显降低。这些发现表明，位于FHH大鼠1号染色体小区域的基因序列变异，通过降低其抑制BK通道活性、膜去极化和抑制胞质钙浓度上升的能力，损害了5- ht介导的血管收缩。
Previous studies suggest that middle cerebral arteries (MCAs) of Fawn Hooded Hypertensive (FHH) rats exhibit impaired myogenic response and introgression of a small region of Brown Norway chromosome 1 containing 15 genes restored the response in FHH.1BN congenic rat. The impaired myogenic response in FHH rats is associated with an increase in the activity of the large conductance potassium (BK) channel in vascular smooth muscle cells (VSMCs). The present study examined whether the increased BK channel function in FHH rat alters vasoconstrictor response to serotonin (5-HT). Basal myogenic tone and spontaneous myogenic response of the MCA was attenuated by about twofold and about fivefold, respectively in FHH compared with FHH.1BN rats. 5-HT (0.1 μM)-mediated vasoconstriction was about twofold lower, and inhibition of the BK channel increased the vasoconstrictor response by about threefold in FHH compared with FHH.1BN rats. 5-HT (3 μM) decreased BK channel and spontaneous transient outward currents in VSMCs isolated from FHH.1BN but had no effect in FHH rats. 5-HT significantly depolarized the membrane potential in MCAs of FHH.1BN than FHH rats. Blockade of the BK channel normalized 5-HT-induced depolarization in MCAs of FHH rats. The 5-HT-mediated increase in cytosolic calcium concentration was significantly reduced in plateau phase in the VSMCs of FHH relative to FHH.1BN rats. These findings suggest that sequence variants in the genes located in the small region of FHH rat chromosome 1 impairs 5-HT-mediated vasoconstriction by decreasing its ability to inhibit BK channel activity, depolarize the membrane and blunt the rise in cytosolic calcium concentration.