Stress-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Blockade of Angiotensin-Converting Enzyme or Tumor Necrosis Factor-α.
Stress-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Blockade of Angiotensin-Converting Enzyme or Tumor Necrosis Factor-α.
复制标题
压力诱导的血管紧张素 II 高血压敏化可通过阻断血管紧张素转换酶或肿瘤坏死因子-α 来逆转。
DOI：
10.1093/ajh/hpz075
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发表时间：
2019
影响因子：
3.2
通讯作者：
Johnson,AlanKim
中科院分区：
文献类型：
--
作者：
Xue,Baojian;Yu,Yang;Wei,Shun-Guang;Beltz,TerryG;Guo,Fang;Felder,RobertB;Johnson,AlanKim
创伤后应激障碍（PTSD）的特征是应激反应紊乱，并与心血管疾病风险增加有关。本研究探讨是否血管紧张素（Ang）II引起的高血压反应是致敏的PTSD模型和是否血管紧张素转换酶（ACE）或肿瘤坏死因子（TNF）-α抑制PTSD之前阻断这种增敏的Ang II hypertension. METHODS居民入侵者范式被用来模拟PTSD。每只入侵大鼠（雄性Sprague-Dawley）给予正常饮用水或在饮用水中预先给予ACE抑制剂（captopril）或TNF-α抑制剂（pentaphylline）2周。随后，委员会注意到，他们接触的是另一位居民（雄性Long-Evans）皮下注射Ang II 2周后，应激大鼠对Ang II的高血压反应显著增强，（应激Δ40.2 ± 3.9 mm Hg vs.未应激Δ20.5 ± 4.5 mm Hg）以及肾素-血管紧张素系统（RAS）和促炎细胞因子（PIC）的mRNA或蛋白质表达上调终板和室旁核中的小胶质细胞标记物的变化。无论是用血管紧张素转换酶（ACE）或血管紧张素转换酶（ACE）预处理，（Δ21.3 ± 3.9 mm Hg）或TNF-α抑制剂（Δ21.4 ± 2.6 mm Hg）.结论严重应激引起的脑RAS和PIC的上调参与了创伤诱导的高血压对Ang Ⅱ的敏感性，并且诸如创伤后应激障碍之类的疾病可能使个体易患高血压。
BACKGROUNDPost-traumatic stress disorder (PTSD) is characterized by a disordered stress response and associated with increased cardiovascular disease risk. The present study investigated whether angiotensin (Ang) II-elicited hypertensive response is sensitized in a model of PTSD and whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor (TNF)-α prior to PTSD blocks this sensitization of Ang II hypertension.METHODSThe resident–intruder paradigm was used to model PTSD. Each intruder rat (male Sprague-Dawley) was given normal drinking water or was pretreated with either an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water for 2 weeks. Subsequently, they were exposed to a different resident (male Long-Evans) for 2 hours on 3 days with each session separated by 1 day and then received a subcutaneous infusion of Ang II for 2 weeks.RESULTSThe stressed rats had a significantly enhanced hypertensive response to the Ang II infusion (stressed Δ40.2 ± 3.9 mm Hg vs. unstressed Δ20.5 ± 4.5 mm Hg) and an upregulation of mRNA or protein expression of renin–angiotensin system (RAS) and proinflammatory cytokine (PIC) components and of a microglial marker in the lamina terminalis and hypothalamic paraventricular nucleus when compared with unstressed control rats. Both the sensitized hypertensive response and enhanced gene and protein expression were blocked by pretreatment with either ACE (Δ21.3 ± 3.9 mm Hg) or TNF-α inhibitor (Δ21.4 ± 2.6 mm Hg).CONCLUSIONSThe results indicate that upregulation of the brain RAS and PICs produced by severe stress contributes to traumatic-induced sensitization of hypertensive response to Ang II, and disorders such as PTSD may predispose individuals to development of hypertension.