Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, #123, Ta-Pei Road, Niao-Sung District, Kaohsiung, Taiwan.
Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Lipids Health Dis. 2018 Mar 14;17(1):50. doi: 10.1186/s12944-018-0701-0.
Hypertension may result from high-fat (HF) diet induced-obesity and overexposure to glucocorticoids in utero. Recent studies demonstrated the potent contribution of adipose tissue's renin-angiotensin system (RAS) to systemic RAS, which plays a key role in regulating blood pressure (BP). In this study, we investigated the effects of prenatal dexamethasone (DEX) exposure and postnatal HF diet on RAS of adipose tissue.
RAS and BP of 6-month old rats exposed to prenatal DEX and/or postnatal HF diet were examined.
Prenatal DEX plus postnatal HF exerted a synergistic effect on systolic BP. Prenatal DEX exposure suppressed plasma angiotensin (ANG) I and ANG II, whereas postnatal HF suppressed plasma ANG-(1-7) level. Prenatal DEX increased prorenin receptor and renin levels, but suppressed angiotensinogen (AGT) and angiotensin-converting-enzyme 1 (ACE1) mRNA expressions in adipose tissue. Postnatal HF increased AGT mRNA expression, but suppressed prorenin receptor, renin, ACE2, ANG II type 2 receptor (AT2R), and Mas receptor (MasR) mRNA expression levels.
Prenatal GC exposure altered the ACE1/ANG II/ANG II type 1 receptor (AT1R) axis, whereas postnatal HF negatively impacted the ACE2/ANG-(1-7)/MasR axis. Prenatal DEX exposure and postnatal HF synergistically elevated BP through a distinct programming mechanism of systemic and adipose RAS. Adipose RAS might be a target for precise hypertension treatment.
高血压可能是高脂肪（HF）饮食引起的肥胖和胎儿期糖皮质激素暴露引起的。最近的研究表明，脂肪组织肾素-血管紧张素系统（RAS）对全身 RAS 的强大贡献，在调节血压（BP）方面起着关键作用。在这项研究中，我们研究了产前地塞米松（DEX）暴露和产后 HF 饮食对脂肪组织 RAS 的影响。
检查了暴露于产前 DEX 和/或产后 HF 饮食的 6 个月大大鼠的 RAS 和 BP。
产前 DEX 加产后 HF 对收缩压有协同作用。产前 DEX 暴露抑制了血浆血管紧张素（ANG）I 和 ANG II，而产后 HF 抑制了血浆 ANG-（1-7）水平。产前 DEX 增加了前肾素受体和肾素水平，但抑制了脂肪组织中的血管紧张素原（AGT）和血管紧张素转换酶 1（ACE1）mRNA 表达。产后 HF 增加了 AGT mRNA 表达，但抑制了前肾素受体、肾素、ACE2、ANG II 型 2 受体（AT2R）和 Mas 受体（MasR）mRNA 表达水平。
产前 GC 暴露改变了 ACE1/ANG II/ANG II 型 1 受体（AT1R）轴，而产后 HF 则通过系统和脂肪 RAS 的独特编程机制对 ACE2/ANG-（1-7）/MasR 轴产生负面影响。产前 DEX 暴露和产后 HF 通过系统和脂肪 RAS 的独特编程机制协同升高血压。脂肪 RAS 可能是精确治疗高血压的靶点。
