New insights into the importance of aminopeptidase A in hypertension
New insights into the importance of aminopeptidase A in hypertension
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DOI：
10.1007/s10741-007-9065-7
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发表时间：
2008-09-01
影响因子：
4.6
通讯作者：
Wright, John W.
中科院分区：
文献类型：
--
作者：
Mizutani, Shigehiko;Ishii, Masakazu;Wright, John W.
肾素-血管紧张素系统（RAS）在维持正常血压和高血压的病因学中起重要作用;然而，很少关注效应肽血管紧张素II（AngII）的降解。由于氨肽酶A（阿帕）缺陷小鼠发展为高血压阿帕似乎是通过降解AngII控制血压的必需酶。在自发性高血压大鼠（SHR）中观察到的强烈高血压是由于RAS的激活以及伴随的肾脏阿帕的降低。在Goldblatt高血压模型和Dahl盐敏感（DSS）大鼠中，还测量了RAS激活期间阿帕的变化。DSS大鼠在高血压发作时显示肾阿帕活性升高，表明对循环AngII升高具有保护作用，随后随着高血压的进展阿帕活性降低。在先兆子痫期间在人母体血清阿帕活性中观察到的变化与在DSS大鼠模型中在肾阿帕中测量的变化相似。在先兆子痫发作时，阿帕活性高于正常妊娠期间，并且随着先兆子痫的进展（重度先兆子痫）下降至低于正常妊娠期间观察到的水平。血清阿帕活性也增加激素替代治疗（HRT），可能在反应升高的AngII水平。因此，它似乎是重要的，以考虑激活的RAS，循环水平的血管紧张素Ⅱ，阿帕的高血压疾病的可用性之间的关系。
The renin-angiotensin system (RAS) plays an important role in the maintenance of normal blood pressure and the etiology of hypertension; however, minimal attention has been paid to the degradation of the effector peptide, angiotensin II (AngII). Since aminopeptidase A (APA)-deficient mice develop hypertension APA appears to be an essential enzyme in the control of blood pressure via degradation of AngII. The robust hypertension seen in the spontaneously hypertensive rat (SHR) is due to activation of the RAS, and an accompanying decrease in kidney APA. Changes in APA have also been measured during the activation of the RAS in the Goldblatt hypertension model and Dahl salt-sensitive (DSS) rat. The DSS rat shows an elevation in renal APA activity at the onset of hypertension suggesting a protective role against elevations in circulating AngII, followed by decreased APA activity with advancing hypertension. Changes seen in human maternal serum APA activity during preeclampsia are similar to changes measured in renal APA in the DSS rat model. APA activity is higher than during normal pregnancy at the onset of preeclampsia, and with advancing preeclampsia (severe preeclampsia) declines below that seen during normal pregnancy. Serum APA activity is also increased during hormone replacement therapy (HRT), perhaps in reaction to elevated levels of AngII. Thus, it appears important to consider the relationship among activation of the RAS, circulating levels of AngII, and the availability of APA in hypertensive disorders.