Brosnihan K Bridget, Merrill David C, Yamaleyeva Liliya M, Chen Kai, Neves Liomar, Joyner JaNae, Givner Courtney, Lanier Kristy, Moorefield Cheryl, Westwood Brian
Department of Surgery/Hypertension and Vascular Research, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
Aspirus Wausau Medical Center, Wausau, WI, 54401, USA.
Endocrine. 2020 Aug;69(2):410-419. doi: 10.1007/s12020-020-02296-3. Epub 2020 Apr 22.
To address whether differential regulation of the renin-angiotensin-aldosterone system occurs in pre-eclampsia, we performed an analysis of the time course of circulating and urinary profiles of the vasoconstrictor (Ang II) and the vasodilator [Ang-(1-7)] peptides in normal pregnant (NP) and pre-eclamptic (PE) women.
Urine and plasma samples from 86 nulliparous women were collected prospectively; 67 subjects continued as NP and 19 developed PE. Subjects were enrolled prior to 12 weeks of gestation and plasma and spot urine samples were obtained throughout gestation. Control samples were obtained at 6 weeks postpartum (PP).
Mean blood pressure (p < 0.001) was elevated at 31-37 weeks of gestation in PE subjects as compared with NP subjects. Plasma Ang I and Ang II levels were elevated in NP subjects as early as 16 weeks of gestation and maintained throughout gestation. In PE subjects both plasma Ang I and Ang II were elevated at 16-33 weeks as compared with PP levels. PE subjects showed reduced plasma Ang I and Ang II (at 35-37 weeks of gestation) compared with NP subjects. Plasma Ang-(1-7) was unchanged in both groups. All three urinary peptides increased throughout gestation in NP subjects. In PE subjects urinary Ang I was increased at 23-26 weeks and was maintained throughout gestation. Urinary Ang II was increased at 27-29 and 31-33 weeks of gestation. PE subjects had no change in urinary Ang-(1-7).
The activation of the RAS, particularly Ang II throughout normal gestation may contribute to the maintenance of vascular tone during normal pregnancy. However higher sensitivity to Ang II in pre-eclampsia may be potentiated by the higher circulating and urinary levels of Ang II, unopposed by local renal Ang-(1-7), and thus may contribute to the development of pre-eclampsia.
为了探讨子痫前期肾素 - 血管紧张素 - 醛固酮系统是否存在差异调节，我们对正常妊娠（NP）和子痫前期（PE）女性体内血管收缩肽（Ang II）和血管舒张肽[Ang-(1-7)]的循环及尿液水平的时间进程进行了分析。
前瞻性收集了86例未生育女性的尿液和血浆样本；67例受试者持续为正常妊娠，19例发展为子痫前期。受试者在妊娠12周前入组，并在整个妊娠期采集血浆和随机尿样。产后6周（PP）采集对照样本。
与正常妊娠受试者相比，子痫前期受试者在妊娠31 - 37周时平均血压升高（p < 0.001）。正常妊娠受试者血浆Ang I和Ang II水平早在妊娠16周时就升高，并在整个妊娠期维持。与产后水平相比，子痫前期受试者在妊娠16 - 33周时血浆Ang I和Ang II均升高。与正常妊娠受试者相比，子痫前期受试者在妊娠35 - 37周时血浆Ang I和Ang II降低。两组血浆Ang-(1-7)均无变化。正常妊娠受试者的所有三种尿肽在整个妊娠期均增加。子痫前期受试者尿Ang I在妊娠23 - 26周时升高，并在整个妊娠期维持。尿Ang II在妊娠27 - 29周和31 - 33周时升高。子痫前期受试者尿Ang-(1-7)无变化。
肾素 - 血管紧张素系统（RAS）的激活，尤其是在整个正常妊娠期Ang II的激活，可能有助于维持正常妊娠期间的血管张力。然而，子痫前期对Ang II的更高敏感性可能因Ang II循环和尿液水平升高而增强，且局部肾Ang-(1-7)未起到拮抗作用，从而可能导致子痫前期的发生。
