Yamaleyeva Liliya M, Merrill David C, Ebert Thomas J, Smith Thomas L, Mertz Heather L, Brosnihan K Bridget
The Hypertension & Vascular Research Center, Wake Forest School of Medicine , Winston-Salem, NC , USA .
Hypertens Pregnancy. 2014 Nov;33(4):375-88. doi: 10.3109/10641955.2014.911884. Epub 2014 May 19.
To understand the role of Angiotensin-(1-7) (Ang-(1-7)) in vasculature of pregnant women, we compared cardiac output (CO), total peripheral resistance (TPR) and forearm blood flow (FBF) responses to Ang-(1-7) infusion between normotensive pregnant women in their third trimester and healthy age matched non-pregnant women. The responses of skin microcirculation to Ang-(1-7) were tested in preeclamptic, normotensive pregnant and non-pregnant women. Responses to Angiotensin II (Ang II) were also determined.
Non-invasive methods for systemic (bioimpedance and VascuMAP), FBF (venous occlusion strain gauge plethysmography), and skin (laser Doppler) hemodynamics assessments were used.
Compared to non-pregnant women, systemic infusion of Ang-(1-7) (2000 pmol/min) resulted in a greater increase in CO (9.4 ± 6.4 versus -3.3 ± 2.1%, n = 9-10) in normotensive pregnant women. Brachial local infusion of Ang-(1-7) had no effect on FBF in either group. In non-pregnant and normotensive pregnant women, local Ang II induced a dose-dependent decrease in FBF and increase in forearm resistance at 50 and 100 pmol/min (p < 0.05 versus corresponding baseline, n = 7-10). Following iontophoretic application of 5 mmol/l dose of Ang-(1-7), the change in skin flow was higher in normotensive pregnant versus preeclamptic women (182.5 ± 93 versus 15.76 ± 19.46%, n = 14-15). Skin flow was lower in normotensive pregnant versus preeclamptic women (-46.5 ± 48.7 versus 108.7 ± 49.1%, n = 14-15) following Ang II infusion at 1.0 pmol/min.
In the third trimester of pregnancy, Ang-(1-7) induces alterations in CO and differentially regulates micro- and macro-circulations, depending on the dose. Dysregulation in skin vasculature may contribute to the development of vascular dysfunction and hypertension in preeclampsia.
为了解血管紧张素 -(1 - 7)(Ang -(1 - 7))在孕妇血管系统中的作用,我们比较了妊娠晚期血压正常的孕妇与年龄匹配的健康非孕妇在输注Ang -(1 - 7)后心输出量(CO)、总外周阻力(TPR)和前臂血流量(FBF)的反应。在子痫前期、血压正常的孕妇和非孕妇中测试了皮肤微循环对Ang -(1 - 7)的反应。还测定了对血管紧张素II(Ang II)的反应。
采用无创方法进行全身(生物阻抗和VascuMAP)、FBF(静脉阻塞应变片体积描记法)和皮肤(激光多普勒)血流动力学评估。
与非孕妇相比,血压正常的孕妇全身输注Ang -(1 - 7)(2000 pmol/min)导致CO有更大的增加(9.4±6.4对 - 3.3±2.1%,n = 9 - 10)。两组中,肱动脉局部输注Ang -(1 - 7)对FBF均无影响。在非孕妇和血压正常的孕妇中,局部Ang II在50和100 pmol/min时可引起FBF剂量依赖性降低和前臂阻力增加(与相应基线相比,p < 0.05,n = 7 - 10)。在离子电渗法应用5 mmol/l剂量的Ang -(1 - 7)后,血压正常的孕妇皮肤血流变化高于子痫前期孕妇(182.5±93对15.76±19.46%,n = 14 - 15)。在以1.0 pmol/min输注Ang II后,血压正常的孕妇皮肤血流低于子痫前期孕妇( - 46.5±48.7对108.7±49.1%,n = 14 - 15)。
在妊娠晚期,Ang -(1 - 7)可引起CO改变,并根据剂量差异调节微循环和大循环。皮肤血管系统的调节异常可能导致子痫前期血管功能障碍和高血压的发生。