Maternal separation-induced increases in vascular stiffness are independent of circulating angiotensinogen levels.
Maternal separation-induced increases in vascular stiffness are independent of circulating angiotensinogen levels.
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母体分离引起的血管僵硬度增加与循环血管紧张素原水平无关。
DOI：
10.1152/japplphysiol.00703.2019
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Loria,AnaliaS
中科院分区：
文献类型：
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作者：
Mahanes,TimothyM;Murphy,MargaretO;Ouyang,An;Yiannikouris,FrederiqueB;Fleenor,BradleyS;Loria,AnaliaS
肾素-血管紧张素系统（RAS）前体血管紧张素原（AGT）与高脂肪饮食（HFD）引起的血管壁功能和机械改变有关。先前，我们发现HFD加剧了暴露于母体分离（MatSep）的雄性大鼠的血管紧张素ii诱导的离体主动脉环收缩，这是一种早期生活压力模型。因此，本研究的目的是研究MatSep是否会增加喂食HFD大鼠的AGT分泌，从而促进血管僵硬。雄性Wistar-Kyoto MatSep子代分离（3小时/天，出生后2-14天），以未受干扰的同窝鼠作为对照。在断奶时，大鼠分别饲喂正常饮食（ND）和高热量饮食（HFD） 17周，脂肪热量分别为18%和60%。在血浆中，MatSep降低AGT浓度有主要作用（P< 0.05），日粮对AGT浓度无影响。在尿中，nd喂养的MatSep大鼠显示出更高的AGT浓度，HFD进一步升高了AGT浓度（P< 0.05）。与对照组相比，hfd喂养的MatSep大鼠脂肪组织中AGT mRNA丰度和蛋白表达均升高（P< 0.05）。各组间肝、肾AGT水平无显著差异。此外，MatSep增强了nd喂养大鼠新鲜分离的主动脉环的血管硬度（P< 0.05），而HFD并未使MatSep或对照大鼠的血管硬度恶化。nd喂养大鼠血浆AGT与血管硬度无相关性；但仅在饲喂hfd的MatSep大鼠中呈负相关（P< 0.05）。因此，本研究表明，matsep诱导的血管硬度增加与饮食或血浆AGT无关。新的和值得注意的是，这项研究表明，在暴露于早期生活压力和喂食正常饮食的大鼠中，血管紧张素原（AGT）循环水平与血管僵硬的发展没有相关性。该研究还表明，在高脂肪饮食的大鼠中，早期应激诱导的对血管紧张素II的超敏性血管收缩与AGT的循环水平无关，并且在没有血管僵硬进一步发展的情况下发生。我们的数据显示，早期生活的压力使脂肪组织以性别和物种无关的方式分泌AGT。
The renin-angiotensin system (RAS) precursor angiotensinogen (AGT) has been implicated in the functional and mechanical alterations of the vascular wall in response to high-fat diet (HFD). Previously, we showed that HFD exacerbates angiotensin II-induced constriction in isolated aortic rings from male rats exposed to maternal separation (MatSep), a model of early-life stress. Thus, the aim of this study was to investigate whether MatSep increases AGT secretion promoting vascular stiffness in rats fed a HFD. Male Wistar-Kyoto MatSep offspring were separated (3 h/day, postnatal days 2–14), and undisturbed littermates were used as controls. At weaning, rats were fed for 17 wk a normal diet (ND) or a HFD, 18% or 60% kcal from fat, respectively. In plasma, there was a main effect of MatSep reducing AGT concentration (P< 0.05) but no effect due to diet. In urine, ND-fed MatSep rats displayed higher AGT concentrations that were further increased by HFD (P< 0.05 vs. control). AGT mRNA abundance and protein expression were increased in adipose tissue from HFD-fed MatSep rats compared with control rats (P< 0.05). No significant differences in liver and kidney AGT levels were found between groups. In addition, MatSep augmented vascular stiffness assessed on freshly isolated aortic rings from ND-fed rats (P< 0.05), yet HFD did not worsen vascular stiffness in either MatSep or control rats. There was no correlation between plasma AGT and vascular stiffness in ND-fed rats; however, this relationship was negative in HFD-fed MatSep rats only (P< 0.05). Therefore, this study shows that MatSep-induced increases in vascular stiffness are independent of diet or plasma AGT.NEW & NOTEWORTHYThis study demonstrates that there was no correlation between circulating levels of angiotensinogen (AGT) and the development of vascular stiffness in rats exposed to early-life stress and fed a normal diet. This study also shows that early-life stress-induced hypersensitive vascular contractility to angiotensin II in rats fed a high-fat diet is independent of circulating levels of AGT and occurs without further progression of vascular stiffness. Our data show that early-life stress primes the adipose tissue to secrete AGT in a sex- and species-independent fashion.