Kidney aminopeptidase A and hypertension, part I - Spontaneously hypertensive rats
Kidney aminopeptidase A and hypertension, part I - Spontaneously hypertensive rats
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DOI：
10.1161/01.hyp.33.2.740
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发表时间：
1999-02-01
期刊：
影响因子：
8.3
通讯作者：
Song, LJ
中科院分区：
文献类型：
--
作者：
Healy, DP;Song, LJ
在自发性高血压大鼠 (SHR) 及其正常血压对照品系中，在对应于高血压前期（4 周）、发展期（8 周）和确立期（16 周）的 3 个不同年龄阶段，测量了氨肽酶 A (APA) 的组织和血浆水平，氨肽酶 APA 是将血管紧张素 II (Ang II) 水解为血管紧张素 III 的主要酶。与血压正常的 Wistar-Kyoto 大鼠相比，SM 在所有 3 个年龄段的血浆 APA 活性均显着但适度升高。同样，在所有年龄段的 SHR 中，大脑、心脏和肾上腺中的 APA 水平普遍升高，但同样只是中度升高。然而，肾脏内的 APA 活性大幅增加，其中 SHR 中的 APA 水平在 3、8 和 16 周龄时分别升高了 41%、51% 和 68%。 8 周和 16 周龄 SHR 的免疫印迹中，肾脏 APA 水平也显着增加。与 Wistar-Kyoto 大鼠相比，从 16 周龄 SHR 分离的肾小球 APA 活性高出 57%，免疫反应性也增强。为了确定 SHR 中肾脏 APA 活性的增加是否与 Ang II 水平相关，用血管紧张素转换酶抑制剂卡托普利治疗 SHR 2 周。卡托普利治疗将血压降低至正常血压值，并导致肾脏 APA 活性降低 25%。这些结果表明，肾脏中 APA 的表达可能受到肾素-血管紧张素系统活性的调节。如果是这样，这将进一步表明，在 Ang Ii 水平升高的情况下，APA 的上调将对 Ang II 介导的心血管疾病具有保护作用，而 APA 表达的减少或上调失败会加剧此类情况。
Tissue and plasma levels of aminopeptidase A (APA), the principal enzyme that hydrolyzes angiotensin II (Ang II) to angiotensin III, were measured in spontaneously hypertensive rats (SHR) and their normotensive control strain at 3 different ages corresponding to prehypertensive (4 weeks), developing (8 weeks), and established (16 weeks) phases of hypertension. Plasma APA activity was significantly but modestly elevated in SM at all 3 ages compared with normotensive Wistar-Kyoto rats. Likewise, levels of APA in brain, heart, and adrenal gland were generally, but again only moderately, elevated in SHR at all ages. However, a large increase in APA activity was seen within the kidney in which APA levels were elevated 41%, 51%, and 68% in SHR at 3, 8, and 16 weeks of age, respectively. Kidney APA levels were also significantly increased in immunoblots from 8- and 16-week-old SHR. Glomeruli isolated from 16-week-old SHR had 57% higher APA activity and increased immunoreactivity compared with Wistar-Kyoto rats. To determine whether the increase in kidney APA activity in SHR was related to Ang II levels, SHR were treated for 2 weeks with the angiotensin-converting enzyme inhibitor captopril. Captopril treatment reduced blood pressure to normotensive values and resulted in a 25% reduction in kidney APA activity, These results suggest that APA expression in the kidney may be regulated by activity of the renin-angiotensin system. If so, this would further suggest that upregulation of APA during conditions in which Ang Ii levels were elevated would have a protective effect against Ang II-mediated cardiovascular diseases, whereas a decrease in APA expression or a failure to upregulate would exacerbate such conditions.