Female Mice Exposed to Postnatal Neglect Display Angiotensin II-Dependent Obesity-Induced Hypertension.
Female Mice Exposed to Postnatal Neglect Display Angiotensin II-Dependent Obesity-Induced Hypertension.
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产后忽视的雌性小鼠表现出血管紧张素 II 依赖性肥胖诱发的高血压。
DOI：
10.1161/jaha.119.012309
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发表时间：
2019
影响因子：
5.4
通讯作者：
Loria,AnaliaS
中科院分区：
文献类型：
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作者：
Dalmasso,Carolina;Leachman,JacquelineR;Ensor,CharlesM;Yiannikouris,FrederiqueB;Giani,JorgeF;Cassis,LisaA;Loria,AnaliaS
背景我们以前曾报道过，暴露于母亲分离和早期断奶（MSEW）的雌性小鼠，一种早期生活应激模型，表现出与高血压相关的饮食诱导的肥胖加剧。本研究的目的是测试是否MSEW促进血管紧张素II依赖性高血压通过激活的renin-angiotensin system in adipose tissue.Methods和ResultsMSEW实现了每天分离的母亲和断奶在出生后第17天，而正常饲养的对照组断奶在出生后第21天。雌性对照和MSEW断奶仔猪接受低脂饲料（LF，10% kcal脂肪）或高脂饲料（HF，60% kcal脂肪）20周。与对照组相比，MSEW对LF喂养小鼠的平均动脉压无明显影响，但对HF喂养小鼠的平均动脉压有明显升高（P<0.05）。与对照组相比，MSEW小鼠血浆和脂肪组织中血管紧张素II浓度升高（P<0.05）。此外，血管紧张素原浓度仅在MSEW小鼠的脂肪组织中增加（P<0.05），而血管紧张素转换酶蛋白表达和活性在组间相似。慢性依那普利治疗（2.5 mg/kg/天，饮用水，7天）降低了两组喂食HF的小鼠的平均动脉压（P<0.05），并消除了MSEW造成的差异。急性血管紧张素II诱导的平均动脉压升高（10 μg/kg SC）在未处理的MSEW HF喂养小鼠中与对照组相比有所减弱（P<0.05）;然而，依那普利处理的小鼠组间的反应相似。
BackgroundWe have previously reported that female mice exposed to maternal separation and early weaning (MSEW), a model of early life stress, show exacerbated diet‐induced obesity associated with hypertension. The goal of this study was to test whether MSEW promotes angiotensin II–dependent hypertension via activation of the renin‐angiotensin system in adipose tissue.Methods and ResultsMSEW was achieved by daily separations from the dam and weaning at postnatal day 17, while normally reared controls were weaned at postnatal day 21. Female controls and MSEW weanlings were placed on a low‐fat diet (LF, 10% kcal from fat) or high‐fat diet (HF, 60% kcal from fat) for 20 weeks. MSEW did not change mean arterial pressure in LF–fed mice but increased it in HF–fed mice compared with controls (P<0.05). In MSEW mice fed a HF, angiotensin II concentration in plasma and adipose tissue was elevated compared with controls (P<0.05). In addition, angiotensinogen concentration was increased solely in adipose tissue from MSEW mice (P<0.05), while angiotensin‐converting enzyme protein expression and activity were similar between groups. Chronic enalapril treatment (2.5 mg/kg per day, drinking water, 7 days) reduced mean arterial pressure in both groups of mice fed a HF (P<0.05) and abolished the differences due to MSEW. Acute angiotensin II–induced increases in mean arterial pressure (10 μg/kg SC) were attenuated in untreated MSEW HF–fed mice compared to controls (P<0.05); however, this response was similar between groups in enalapril‐treated mice.ConclusionsThe upregulation of angiotensinogen and angiotensin II in adipose tissue could be an important mechanism by which female MSEW mice fed a HF develop hypertension.