Jerat S, Morrish D W, Davidge S T, Kaufman S
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Hypertension. 2001 Feb;37(2):227-31. doi: 10.1161/01.hyp.37.2.227.
Adrenomedullin is a potent vasodilatory peptide with plasma levels that increase during pregnancy. Although fetoplacental adrenomedullin levels are reported to increase in preeclampsia, maternal plasma levels may be elevated or decreased, or they may resemble those in normal pregnancy. In other hypertensive conditions, adrenomedullin increases. Therefore, we hypothesized that maternal plasma adrenomedullin levels would be higher in hypertensive pregnancies than in normotensive pregnancies and that the higher placental resistance found in preeclamptic pregnancies results from blunted activity of adrenomedullin on the vasculature. Adrenomedullin concentrations in plasma from women with normotensive pregnancies, gestational hypertension, and preeclampsia were determined by radioimmunoassay. Stem villous arteries from normotensive and preeclamptic pregnancies were dissected and mounted on a wire myograph system. Arteries were first preconstricted to 80% of their maximum constriction with U46619, a thromboxane A(2) mimetic, and exposed to cumulative doses of adrenomedullin (1x10(-)(9) to 3x10(-)(7) mol/L). Contrary to our hypothesis, there were no significant differences in maternal plasma adrenomedullin levels among patients with normal pregnancies, gestational hypertension, and preeclampsia. Adrenomedullin significantly relaxed arteries from both normal and preeclamptic placentas, but there was no significant difference between the 2 groups. During normal pregnancy, adrenomedullin may contribute to the low placental vascular resistance. This pathway appears to be intact in preeclampsia. We conclude that the increased placental vascular resistance observed in preeclampsia is due neither to reduced adrenomedullin secretion nor to an attenuated vascular responsiveness. Moreover, unlike other hypertensive disorders, there is no compensatory rise in circulating adrenomedullin levels.
肾上腺髓质素是一种强效血管舒张肽，其血浆水平在孕期会升高。尽管据报道子痫前期患者胎盘-胎儿肾上腺髓质素水平会升高，但母体血浆水平可能升高、降低或与正常妊娠时相似。在其他高血压疾病中，肾上腺髓质素水平会升高。因此，我们推测高血压妊娠患者的母体血浆肾上腺髓质素水平会高于正常血压妊娠患者，且子痫前期妊娠中发现的较高胎盘阻力是由于肾上腺髓质素对血管系统的活性减弱所致。通过放射免疫分析法测定了正常血压妊娠、妊娠期高血压和子痫前期女性的血浆肾上腺髓质素浓度。解剖了正常血压和子痫前期妊娠的绒毛干动脉，并将其安装在血管张力测定系统上。首先用血栓素A2模拟物U46619将动脉预收缩至其最大收缩力的80%，然后给予累积剂量的肾上腺髓质素（1×10−9至3×10−7 mol/L）。与我们的假设相反，正常妊娠、妊娠期高血压和子痫前期患者的母体血浆肾上腺髓质素水平没有显著差异。肾上腺髓质素可使正常和子痫前期胎盘的动脉显著舒张，但两组之间无显著差异。在正常妊娠期间，肾上腺髓质素可能有助于维持较低的胎盘血管阻力。子痫前期时该途径似乎完好无损。我们得出结论，子痫前期观察到的胎盘血管阻力增加既不是由于肾上腺髓质素分泌减少，也不是由于血管反应性减弱。此外，与其他高血压疾病不同，循环肾上腺髓质素水平没有代偿性升高。
