Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring.
Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring.
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阻断血管紧张素转换酶或肿瘤坏死因子-α 可逆转母体高脂肪饮食诱导的雄性大鼠后代血管紧张素 II 高血压的敏感性。
DOI：
10.1152/ajpregu.00200.2019
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Xue,Baojian
中科院分区：
文献类型：
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作者：
Wang,Xue-Fang;Li,Jian-Dong;Huo,Yan-Li;Zhang,Yu-Ping;Fang,Zhi-Qin;Wang,Hai-Ping;Peng,Wei;Johnson,AlanKim;Xue,Baojian
母体高脂饮食与子代成年后代谢综合征和心血管疾病有关。我们以前的研究表明，母亲HFD增强升压反应，血管紧张素II或促炎细胞因子（PIC），这是与增加表达的脑肾素-血管紧张素系统（RAS）组件和PIC在成年后代。本研究进一步研究了抑制血管紧张素转换酶（ACE）或肿瘤坏死因子-α（TNF-α）是否可阻断HFD母鼠后代的ANG II高血压致敏作用。从交配前两周开始，所有后代均由正常脂肪饮食（NFD）或HFD的母鼠饲养，并维持至后代断奶。然后在饮水中加入ACE抑制剂（captopril）或TNF-α抑制剂（pentaphylline），直至试验结束，给予慢升压剂量的ANG II。终板和室旁核的RT-PCR分析显示，与年龄匹配的NFD母鼠的后代相比，HFD母鼠的雄性后代中几种RAS组分和PIC的mRNA表达上调。增强的基因表达通过阻断RAS或PIC而减弱。同样，ANG II给药在HFD母鼠的后代中产生增强的升压反应。ACE或TNF-α抑制剂可消除这种作用。总之，本研究提供了机制证据和治疗策略，即RAS和PIC的全身抑制可以阻断母体HFD诱导的ANG II高血压致敏作用，这与后代脑RAS和PIC表达的减弱有关。
Maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular diseases in adult offspring. Our previous study demonstrated that maternal HFD enhances pressor responses to ANG II or a proinflammatory cytokine (PIC), which is associated with increased expression of brain renin-angiotensin system (RAS) components and PICs in adult offspring. The present study further investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) blocks sensitization of ANG II hypertension in offspring of HFD dams. All offspring were bred from dams with normal fat diet (NFD) or HFD starting two weeks before mating and maintained until weaning of the offspring. Then the weaned offspring were treated with an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water through the end of testing with a slow-pressor dose of ANG II. RT-PCR analyses of the lamina terminalis and paraventricular nucleus revealed upregulation of mRNA expression of several RAS components and PICs in male offspring of HFD dams when compared with age-matched offspring of NFD dams. The enhanced gene expression was attenuated by blockade of either RAS or PICs. Likewise, ANG II administration produced an augmented pressor response in offspring of HFD dams. This was abolished by either ACE or TNF-α inhibitor. Taken together, this study provides mechanistic evidence and a therapeutic strategy that systemic inhibition of the RAS and PICs can block maternal HFD-induced sensitization of ANG II hypertension, which is associated with attenuation of brain RAS and PIC expression in offspring.