17β-estradiol downregulates tissue angiotensin-converting enzyme and ANG II type 1 receptor in female rats
17β-estradiol downregulates tissue angiotensin-converting enzyme and ANG II type 1 receptor in female rats
复制标题
DOI：
10.1152/ajpregu.00595.2004
复制
发表时间：
2005-03-01
影响因子：
2.8
通讯作者：
Leenen, FHH
中科院分区：
文献类型：
--
作者：
Dean, SA;Tan, JH;Leenen, FHH
雌激素与心血管疾病的恶化和预防有关。17 β-雌二醇（E2）对心血管系统的作用可能至少部分通过其对局部组织肾素-血管紧张素系统（RAS）的调节来介导。我们评估了四组雌性Wistar大鼠心脏、肺、腹主动脉、肾上腺、肾脏和大脑中的两种关键成分血管紧张素转换酶（ACE）和血管紧张素Ⅱ 1型受体（AT（1）R（n = 5-6/组）：1）假卵巢切除，2）用皮下载体处理的卵巢切除（OVX），3）用25 μ g/天（常规）E2皮下处理的OVX，和4）OVX用250 μ g/天（高）皮下E2治疗2或5周。2周后，血浆ACE活性不受OVX的影响，但OVX +常规E2和OVX +高E2大鼠的ACE活性比假OVX大鼠低34-38%，5周后这些降低不再存在。5周后，单独OVX可使右心室、左心室、肾、肺、腹主动脉、肾上腺和脑内几个心血管调节核团的ACE活性和结合密度以及AT（1）R结合密度增加15-100%。这些影响，在大多数情况下，防止定期E2补充和逆转减少高E2治疗。组织ACE和AT（1）R的这种调节是重要的，因为这些组织RAS的活性有助于高血压、动脉粥样硬化和心肌梗死后LV重塑的发病机制和/或进展。
Estrogens have been implicated in both worsening and protecting from cardiovascular disease. The effects of 17beta-estradiol (E2) on the cardiovascular system may be mediated, at least in part, by its modulation of local tissue renin-angiotensin systems (RAS). We assessed two critical components, angiotensin-converting enzyme (ACE) and ANG II type 1 receptor (AT(1)R), in the heart, lung, abdominal aorta, adrenal, kidney, and brain in four groups of female Wistar rats (n = 5-6/group): 1) sham ovariectomized, 2) ovariectomized (OVX) treated with subcutaneous vehicle, 3) OVX treated with 25 mug/day (regular) E2 subcutaneously, and 4) OVX treated with 250 mug/day (high) subcutaneous E2 for 2 or 5 wk. After 2 wk, plasma ACE activity was not altered by OVX, but it was 34-38% lower in OVX + regular E2 and OVX + high E2 rats compared with sham OVX rats, and these decreases were no longer present after 5 wk. After 5 wk, OVX alone increased ACE activity and binding densities, and AT(1)R binding densities by 15-100% in right ventricle, left ventricle (LV), kidney, lung, abdominal aorta, adrenal and several cardiovascular regulatory nuclei in the brain. These effects were, for the most part, prevented by regular E2 replacement and were reversed to decreases by high E2 treatment. This regulation of tissue ACE and AT(1)R is significant as the activity of these tissue RAS contributes to the pathogenesis and/or progression of hypertension, atherosclerosis, and LV remodeling after myocardial infarction.