A prospective, longitudinal study of the renin-angiotensin system, prostacyclin and thromboxane in the first trimester of normal human pregnancy: association with birthweight
A prospective, longitudinal study of the renin-angiotensin system, prostacyclin and thromboxane in the first trimester of normal human pregnancy: association with birthweight
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DOI：
10.1093/humrep/dei184
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发表时间：
2005-11-01
影响因子：
6.1
通讯作者：
Pipkin, FB
中科院分区：
文献类型：
--
作者：
Al Kadi, H;Nasrat, H;Pipkin, FB
背景：人类妊娠早期是一种心血管充盈不足的状态。肾素-血管紧张素系统（RAS）直接与钠和水的稳态有关。已知血管紧张素原是妊娠期血管紧张素I和血管紧张素II生成的限速成分。通常测量的“肾素活性”不区分酶和底物。我们假设RAS从怀孕开始就被激活，血浆肾素浓度（PRC）和血管紧张素原将显示差异调节，并可能刺激前列环素的升高。方法：对12名未经产的正常妇女进行前瞻性研究。PRC和血管紧张素原和前列环素和血栓素代谢产物的排泄量在怀孕前和怀孕后4 - 6次至13周进行测量。结果：孕6周时，平均PRC显著升高，并保持稳定至13周。最初的血管紧张素原反应各不相同，但在6-8周后持续升高。回归分析显示，孕早期血管紧张素原与校正出生体重百分位数密切相关（P < 0.001）。类花生酸代谢物的排泄变化很大，但从6周开始显著上升;前列环素和血栓素排泄之间的比例在此期间没有改变。测量的各种激素之间没有相关性。结论：已知血管紧张素原在妊娠中具有限速作用。其与出生体重的相关性可能是通过影响早期血浆容量扩张，并可能与宫内生长受限和先兆子痫有关。
BACKGROUND: Very early human pregnancy is a state of cardiovascular underfilling. The renin-angiotensin system (RAS) is directly concerned with sodium and water homeostasis. Angiotensinogen is known to be the rate-limiting component in the generation of angiotensin I, and hence angiotensin II, in pregnancy. The usual measurement of 'renin activity' does not differentiate between enzyme and substrate. We hypothesized that the RAS is activated from the start of pregnancy; plasma renin concentration (PRC) and angiotensinogen will show differential regulation and might stimulate the rise in prostacyclin. METHODS: A prospective study of 12 nulliparous normal women. PRC and angiotensinogen and excretion of prostacyclin and thromboxane metabolites were measured pre-pregnancy and four to six times after conception to 13 weeks. RESULTS: By 6 weeks gestation, mean PRC was markedly raised and remained stable to 13 weeks. The initial angiotensinogen response varied, but rose consistently after 6-8 weeks. Regression analysis showed angiotensinogen in the first trimester to be strongly associated with corrected birthweight centile (P < 0.001). Excretion of eicosanoid metabolites was very variable, but rose significantly from 6 weeks; the ratio between prostacyclin and thromboxane excretion did not alter over this time. There was no correlation between the various hormones measured. CONCLUSION: Angiotensinogen is known to be rate-limiting in pregnancy. Its association with birthweight may be through effects on early plasma volume expansion and may have implications for intrauterine growth restriction and pre-eclampsia.