Expression of endothelial angiotensin II receptor mRNA in pregnancy-induced hypertension

Am J Hypertens. 2003 Dec;16(12):993-9. doi: 10.1016/j.amjhyper.2003.07.020.

Abstract

Objective: The normal suppression of vascular sensitivity to angiotensin II (Ang II) in pregnancy is lost in pregnancy-induced hypertension (PIH). To examine the mechanism, we investigated Ang II receptor subtype 1 (AT1R) and 2 (AT2R) expression in human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC).

Methods: The HUVEC and VSMC were incubated with serum from normal pregnant women and PIH patients for 0 to 12 h. The AT1R and AT2R mRNA were semiquantified as the ratio to glyceraldehyde-3-phosphate dehydrogenase mRNA, using multiplex reverse transcription-polymerase chain reaction. The AT1R expression was also evaluated by immunocytochemistry.

Results: Serum from PIH patients significantly increased AT1R mRNA of HUVEC (1.48 +/- 0.44) after a 12-h incubation compared with that from normal pregnant women (0.25 +/- 0.14). On the other hand, AT2R mRNA of HUVEC incubated with serum from PIH patients (0.14 +/- 0.02) was significantly decreased compared with HUVEC incubated with serum from normal pregnant women (0.31 +/- 0.08). The AT1R mRNA of VSMC was significantly increased by serum from both PIH patients and normal pregnant women. The AT1R-to-AT2R mRNA ratio increased by serum from PIH patients was significantly reduced by anti-tumor necrosis factor-alpha (TNF-alpha) antibody (20 microg/mL). Valsartan (an AT1R antagonist, at 1 to 10 nmol/L) significantly increased AT2R mRNA of HUVEC. Also, immunocytochemistry demonstrated that endothelial AT1R expression was strongly increased by PIH sera and reduced by anti-TNF-alpha antibody.

Conclusions: Endothelial AT1R expression is increased and AT2R expression is decreased in PIH. The TNF-alpha is related to the pathogenesis of PIH by reduced AT2R mRNA through an increase of AT1R mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Endothelium, Vascular / metabolism*
  • Female
  • Humans
  • Hypertension / metabolism*
  • Muscle, Smooth, Vascular / metabolism
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / metabolism*
  • RNA, Messenger / biosynthesis*
  • Receptors, Angiotensin / biosynthesis*
  • Umbilical Veins / metabolism

Substances

  • RNA, Messenger
  • Receptors, Angiotensin