Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring
Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring
复制标题
DOI：
10.1152/ajpregu.00725.2006
复制
发表时间：
2007-08-01
影响因子：
2.8
通讯作者：
Alexander, Barbara T.
中科院分区：
文献类型：
--
作者：
Grigore, Daniela;Ojeda, Norma B.;Alexander, Barbara T.
大鼠妊娠晚期子宫灌注减少导致宫内生长受限（IUGR），并在4周龄时发生高血压。我们推测，肾素血管紧张素系统（RAS），一个重要的长期控制血压的调节系统，可能是由胎盘功能不全编程，并可能有助于IUGR高血压的病因。我们以前报道过RAS阻断可消除成年IUGR后代的高血压，然而，高血压早期发生的机制尚不清楚。因此，本研究的目的是检查RAS参与早期程序性高血压，并确定是否在IUGR后代中观察到RAS表达的时间变化。出生时肾脏肾素和血管紧张素原mRNA表达显著降低（分别为80%和60%）;血浆和肾脏RAS与高血压无关（平均增加14 mmHg）;但是，在此情况下，高血压（平均增加22 mmHg）与肾血管紧张素转换酶（ACE）活性显著增加（122%）相关肾血管紧张素原mRNA和肾素mRNA（分别为7倍和7.4倍），但肾血管紧张素II或血管紧张素I型受体无变化。ACE抑制剂（依那普利，10 mg中心点/kg中心点/天，从2 ~ 4周龄开始给药）可消除IUGR 4周龄时的高血压（分别降低15 mmHg），而对照后代无显著降压作用。因此，在IUGR后代中观察到肾脏RAS的时间改变，并且可能在IUGR高血压的病因学中起关键作用。
Reduced uterine perfusion initiated in late gestation in the rat results in intrauterine growth restriction (IUGR) and development of hypertension by 4 wk of age. We hypothesize that the renin angiotensin system (RAS), a regulatory system important in the long-term control of blood pressure, may be programmed by placental insufficiency and may contribute to the etiology of IUGR hypertension. We previously reported that RAS blockade abolished hypertension in adult IUGR offspring; however, the mechanisms responsible for the early phase of hypertension are unresolved. Therefore, the purpose of this study was to examine RAS involvement in early programmed hypertension and to determine whether temporal changes in RAS expression are observed in IUGR offspring. Renal renin and angiotensinogen mRNA expression were significantly decreased at birth (80 and 60%, respectively); plasma and renal RAS did not differ in conjunction with hypertension (mean increase of 14 mmHg) in young IUGR offspring; however, hypertension (mean increase of 22 mmHg) in adult IUGR offspring was associated with marked increases in renal angiotensin-converting enzyme (ACE) activity (122%) and renal renin and angiotensinogen mRNA (7-fold and 7.4-fold, respectively), but no change in renal ANG II or angiotensin type I receptor. ACE inhibition (enalapril, 10 mg center dot kg(-1)center dot day(-1), administered from 2 to 4 wk of age) abolished hypertension in IUGR at 4 wk of age (decrease of 15 mmHg, respectively) with no significant depressor effect in control offspring. Therefore, temporal alterations in renal RAS are observed in IUGR offspring and may play a key role in the etiology of IUGR hypertension.