Mizutani Shigehiko, Ishii Masakazu, Hattori Akira, Nomura Seiji, Numaguchi Yasushi, Tsujimoto Masafumi, Kobayshi Hiroshi, Murohara Toyoaki, Wright John W
Department of Medical Science of Proteases, Nagoya University, Graduate School of Medicine, Nagoya, Japan.
Heart Fail Rev. 2008 Sep;13(3):273-84. doi: 10.1007/s10741-007-9065-7. Epub 2007 Nov 8.
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.
肾素-血管紧张素系统（RAS）在维持正常血压及高血压病因学中发挥着重要作用；然而，对于效应肽血管紧张素II（AngII）的降解却极少受到关注。由于氨基肽酶A（APA）缺陷型小鼠会发生高血压，APA似乎是通过降解AngII来控制血压的一种关键酶。自发性高血压大鼠（SHR）中出现的严重高血压是由于RAS激活以及肾脏APA随之减少所致。在Goldblatt高血压模型和Dahl盐敏感（DSS）大鼠的RAS激活过程中也检测到了APA的变化。DSS大鼠在高血压发病初期肾APA活性升高，这表明其对循环中AngII升高具有保护作用，随后随着高血压病情进展，APA活性降低。子痫前期孕妇血清APA活性的变化与DSS大鼠模型中肾APA的变化相似。子痫前期发病时APA活性高于正常妊娠期间，随着子痫前期病情进展（重度子痫前期），其活性降至低于正常妊娠期间的水平。激素替代疗法（HRT）期间血清APA活性也会升高，这可能是对AngII水平升高的一种反应。因此，在高血压疾病中考虑RAS激活、AngII循环水平与APA可用性之间的关系似乎很重要。
