Developmental expression of ACE2 in the SHR kidney: A role in hypertension?
Developmental expression of ACE2 in the SHR kidney: A role in hypertension?
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DOI：
10.1038/sj.ki.5000428
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发表时间：
2006-07-01
影响因子：
19.6
通讯作者：
Thomas, M. C.
中科院分区：
文献类型：
--
作者：
Tikellis, C.;Cooper, M. E.;Thomas, M. C.
肾内肾素-血管紧张素系统（RAS）的异常发育被认为是自发性高血压大鼠（SHR）成年发病高血压的原因之一。血管紧张素转换酶2 （angiotensin converting enzyme, ACE2）是一种与ACE具有互补作用的新型酶。最近的研究表明，ACE2在成人SHR中表达减少。然而，其在高血压前期动物中的调节尚不清楚。在这项研究中，我们研究了ACE2在啮齿动物肾脏中的发育表达及其时间表达，因为它与SHR模型中高血压的发展有关。取SHR大鼠和正常血压Wistar Kyoto （WKY）大鼠（n=8-12/组）在出生、6周龄和成年（80天）时的肾脏进行检查。实时逆转录聚合酶链反应法和猝灭荧光法分别测定ACE2基因表达和活性。通过原位杂交和免疫组织化学方法定位肾脏表达。出生时SHR肾脏中ACE2的表达和活性显著升高。随着高血压的发生，与WKY相比，SHR肾小管中ACE2的表达下降，并且在成人SHR肾中仍然降低。SHR肾小球的表达矛盾地增加。SHR肾脏中ACE2表达的整体发育模式也被改变，在肾脏发育过程中表达下降。SHR肾中ACE2表达的发育模式在高血压发病前发生改变，这与RAS在成人高血压发病机制中的关键作用一致。需要进一步的研究来区分这些变化对该模型中高血压的发生和进展的贡献。
The abnormal development of the intrarenal renin-angiotensin system (RAS) is thought contribute to adult-onset hypertension in the spontaneously hypertensive rat (SHR). Angiotensin-converting enzyme 2 (ACE2) is a novel enzyme with complementary actions to that of ACE. Recent studies have shown that ACE2 expression is reduced in the adult SHR. However, its regulation in pre-hypertensive animals is unknown. In this study, we examine the developmental expression of ACE2 in the rodent kidney and its temporal expression, as it relates to the development of hypertension in the SHR model. Kidneys from SHR and normotensive Wistar Kyoto (WKY) rats (n=8-12/group) at birth, 6 weeks of age, and adulthood (80 days) were examined. Gene expression and activity of ACE2 were determined by real-time reverse transcription-polymerase chain reaction and quenched fluorescence assays, respectively. Renal expression was localized by in situ hybridization and immunohistochemistry. The expression and ACE2 activity are significantly increased in the SHR kidney at birth. With the onset of hypertension, the tubular expression of ACE2 falls in SHR compared to WKY and remains reduced in the adult SHR kidney. Glomerular expression is paradoxically increased in the SHR glomerulus. The overall developmental pattern of ACE2 expression in the SHR kidney is also modified, with declining expression over the course of renal development. The developmental pattern of ACE2 expression in the SHR kidney is altered before the onset of hypertension, consistent with the key role of the RAS in the pathogenesis of adult-onset hypertension. Further research is required to distinguish the contribution of these changes to the development and progression of hypertension in this model.