An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development
An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development
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DOI：
10.1023/a:1006822911586
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发表时间：
1997-11-01
影响因子：
4.3
通讯作者：
Buttar, HS
中科院分区：
文献类型：
--
作者：
Buttar, HS
肾素-血管紧张素系统与许多器官系统中的多种病理生理过程相关，并且已知参与血压的正常调节和肾血管性高血压的发病机制。血管紧张素II是一种多功能激素，通过与两种主要的细胞表面受体亚型（AT（1）和AT（2））相互作用来显示其特性。血管紧张素转换酶（ACE）抑制剂能够改变肾素-血管紧张素系统的作用，并适用于治疗高血压和心脏病。ACE抑制药物的降压作用与其阻断十肽血管紧张素I转化为强效加压八肽血管紧张素II的能力有关。ACE抑制剂与人类的胎儿病和大鼠、兔、绵羊和狒狒的围产期死亡有关。妊娠第26周左右给予ACE抑制剂时，会出现人类胎儿病变。对婴儿的主要不良反应包括：羊水过少、肾小管发育不全、新生儿无尿、颅骨和肺发育不全、轻度至重度宫内发育迟缓、持续性动脉导管未闭和胎儿或新生儿死亡。这些发育异常被认为部分是由于ACE抑制剂对胎儿肾素-血管紧张素系统的直接作用，部分是由于母体低血压导致的缺血以及胎儿-胎盘血流和向胎儿输送的氧气/营养物质减少。本综述的目的是简要讨论肾素-血管紧张素系统的病理生理作用，ACE抑制剂在妊娠患者中的治疗用途，并主要关注ACE抑制剂在人类和动物模型中遇到的主要胎儿毒性作用，我还将回顾我们最近的数据，（captopril +氢氯噻嗪）不仅产生羊水过少，而且扰乱大鼠母体血浆和羊水中葡萄糖和NaCl的平衡。
The renin-angiotensin system is associated with a variety of pathophysiological processes in many organ systems, and is known to be involved in the normal regulation of blood pressure and in the pathogenesis of renovascular hypertension. Angiotensin II is a multifunctional hormone that manifests its properties by interacting with two major subtypes of cell surface receptors (AT(1) and AT(2)). Angiotensin converting enzyme (ACE) inhibitors are able to modify the actions of the renin-angiotensin system, and are indicated for the treatment of hypertension and heart disease. The antihypertensive effects of ACE inhibiting drugs are related to their ability to block the conversion of the decapeptide, angiotensin I, to the potent presser octapeptide, angiotensin II. ACE inhibitors have been implicated in fetopathies in humans and perinatal mortality in rats, rabbits, sheep and baboons. Human fetopathies were seen when ACE inhibitors were given around the 26th week of gestation. The major adverse effects in babies include: oligohydramnios, renal tubular dysgenesis, neonatal anuria, calvarial and pulmonary hypoplasia, mild to severe intrauterine growth retardation, persistent patent ductus arteriosus and fetal or neonatal death. These developmental anomalies are thought to be partly due to a direct action of ACE inhibitors on the fetal renin-angiotensin system and partly due to the ischemia resulting from maternal hypotension and decreases in fetal-placental blood flow and oxygen/ nutrient delivery to the fetus. The purpose of this review is to briefly discuss the pathophysiological role of the renin-angiotensin system, the therapeutic uses of ACE inhibitors in pregnant patients and to focus primarily on the major fetotoxic effects of ACE inhibitors encountered in humans and animal models, I will also review our recent data which show that capozide (captopril + hydrochlorothiazide) not only produces oligohydramnios but also disturbs the balance of glucose and NaCl in the maternal plasma and amniotic fluid of the rat.