Angiotensin-converting enzyme 2 (ACE2) and ACE activities display tissue-specific sensitivity to undernutrition-programmed hypertension in the adult rat
Angiotensin-converting enzyme 2 (ACE2) and ACE activities display tissue-specific sensitivity to undernutrition-programmed hypertension in the adult rat
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DOI：
10.1161/01.hyp.0000185148.27901.fe
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发表时间：
2005-11-01
期刊：
影响因子：
8.3
通讯作者：
Vieau, D
中科院分区：
文献类型：
--
作者：
Rivière, G;Michaud, A;Vieau, D
人类流行病学研究表明，低出生体重与成年后的高血压有关。啮齿类动物的宫内发育迟缓（IUGR）模型支持这些发现，因为营养不良的母鼠的后代会患上高血压。血管紧张素转换酶2（ACE 2）是新近发现的一种与血管紧张素转换酶竞争水解血管紧张素肽的肾素-血管紧张素系统（RAS）组分，因此可调节血压。然而，ACE 2在高血压规划中的潜在参与仍然未知，尽管在IUGR模型中报告了RAS改变。因此，我们首先研究了大鼠中ACE 2和ACE的组织分布，然后研究了高血压编程是否对这两种酶产生差异性影响。采用多重RT-PCR和原位杂交，我们发现ACE 2 mRNA广泛表达和coregionalized与ACE。此外，参与血压稳态的组织（肺、心脏和肾脏）表达高水平的两种酶。酶法检测表明，ACE 2和ACE在这些组织中是协同活性的。整个妊娠期70%食物限制母鼠（FR 30大鼠）的成年（4月龄）后代表现出轻度高血压、肾形态受损。以及升高的血浆血管紧张素11和醛固酮，提示系统性RAS的改变。在FR 30大鼠中，我们发现ACE 2和ACE活性仅在肺中增加，而它们的mRNA表达没有显著改变，表明酶显示组织特异性对编程的敏感性。我们的研究结果表明，ACE 2和ACE在许多大鼠组织中共表达，并且它们在FR 30大鼠肺中的活性增加可能参与高血压编程。
Human epidemiological studies have shown that low birth weight is associated with hypertension in adulthood. Rodent models of intrauterine growth retardation (IUGR) support these findings because offspring from undernourished dams develop hypertension. Angiotensin-converting enzyme 2 (ACE2) is a newly described renin-angiotensin system (RAS) component that competes with ACE for angiotensin peptide hydrolysis and therefore may modulate blood pressure. However, ACE2 potential participation in hypertension programming remains unknown, although RAS alterations were reported in IUGR models. Hence, we first investigated the tissue distribution of ACE2 and ACE in the rat and then whether hypertension programming differentially affects both enzymes. Using multiplex RT-PCR and in situ hybridization, we show that ACE2 mRNA is widely expressed and coregionalized with ACE. Moreover, tissues involved in blood pressure homeostasis (lung, heart, and kidney) express high levels of both enzymes. Enzymatic assays reveal that ACE2 and ACE are coactive in these tissues. Adult (4-month-old) offspring from 70% food-restricted dams throughout gestation (FR30 rats) present mild hypertension, impaired renal morphology. as well as elevated plasma angiotensin 11 and aldosterone, suggesting alterations of the systemic RAS. In FR30 rats, we show that ACE2 and ACE activities are increased only in the lung, whereas their mRNA expression is not significantly altered, showing that the enzymes display tissue-specific sensitivity to programming. Our results indicate that ACE2 and ACE are coexpressed in numerous rat tissues and that their increased activity in the lung of FR30 rats may participate in hypertension programming.