Angiotensin converting enzyme 2 contributes to sex differences in the development of obesity hypertension in C57BL/6 mice.
Angiotensin converting enzyme 2 contributes to sex differences in the development of obesity hypertension in C57BL/6 mice.
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DOI：
10.1161/atvbaha.112.248559
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
Cassis LA
中科院分区：
文献类型：
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作者：
Gupte M;Thatcher SE;Boustany-Kari CM;Shoemaker R;Yiannikouris F;Zhang X;Karounos M;Cassis LA
肥胖促进高血压，但目前尚不清楚肥胖相关的高血压是否存在性别差异。血管紧张素转换酶2（ACE 2）将血管紧张素II（AngII）转化为血管紧张素-（1-7）（Ang-[1-7]），控制肽平衡。我们假设高脂饮食和性激素对ACE 2的组织特异性调节有助于肥胖-高血压的性别差异。HF喂养的女性获得更多的体重和脂肪量比男性。HF喂养的男性肾脏ACE 2活性降低，血浆血管紧张素II水平升高，血浆Ang-（1-7）水平降低。相反，HF喂养的女性表现出脂肪ACE 2活性升高，血浆Ang-（1-7）水平升高。HF喂养的男性有升高的收缩压和舒张压，氯沙坦消除。相比之下，HF喂养的雌性动物在给予Ang-（1-7）受体拮抗剂D-Ala-Ang-（1-7）之前没有表现出收缩压升高。ACE 2的缺乏增加HF喂养的男性和女性的收缩压，这是由氯沙坦消除。HF喂养的雌性小鼠的卵巢切除降低了脂肪ACE 2活性和血浆Ang-（1-7）水平，并促进了肥胖-高血压。最后，雌激素，而不是其他性激素，增加脂肪细胞ACE 2 mRNA丰度。这些结果表明，饮食和性激素对ACE 2的组织特异性调节有助于肥胖-高血压的性别差异。
Obesity promotes hypertension, but it is unclear if sex differences exist in obesity-related hypertension. Angiotensin converting enzyme 2 (ACE2) converts angiotensin II (AngII) to angiotensin-(1–7) (Ang-[1–7]), controlling peptide balance. We hypothesized that tissue-specific regulation of ACE2 by high-fat (HF) feeding and sex hormones contributes to sex differences in obesity-hypertension. HF-fed females gained more body weight and fat mass than males. HF-fed males exhibiting reduced kidney ACE2 activity had increased plasma angiotensin II levels and decreased plasma Ang-(1–7) levels. In contrast, HF-fed females exhibiting elevated adipose ACE2 activity had increased plasma Ang-(1–7) levels. HF-fed males had elevated systolic and diastolic blood pressure that were abolished by losartan. In contrast, HF-fed females did not exhibit increased systolic blood pressure until females were administered the Ang-(1–7) receptor antagonist, D-Ala-Ang-(1–7). Deficiency of ACE2 increased systolic blood pressure in HF-fed males and females, which was abolished by losartan. Ovariectomy of HF-fed female mice reduced adipose ACE2 activity and plasma Ang-(1–7) levels, and promoted obesity-hypertension. Finally, estrogen, but not other sex hormones, increased adipocyte ACE2 mRNA abundance. These results demonstrate that tissue-specific regulation of ACE2 by diet and sex hormones contributes to sex differences in obesity-hypertension.