Endothelium-Dependent Relaxation and Angiotensin II Sensitivity in Experimental Preeclampsia

Anne Marijn van der Graaf*, Marjon J. Wiegman, Torsten Plosch, Gerda G. Zeeman, Azuwerus van Buiten, Robert H. Henning, Hendrik Buikema, Marijke M. Faas

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Objective: We investigated endothelial dysfunction and the role of angiotensin (Ang)-II type I (AT1-R) and type II (AT2-R) receptor in the changes in the Ang-II sensitivity in experimental preeclampsia in the rat.

Methods: Aortic rings were isolated from low dose lipopolysaccharide (LPS) infused pregnant rats (experimental preeclampsia; n=9), saline-infused pregnant rats (n=8), and saline (n=8) and LPS (n=8) infused non-pregnant rats. Endothelium-dependent acetylcholine--mediated relaxation was studied in phenylephrine-preconstricted aortic rings in the presence of vehicle, N-G-nitro-L-arginine methyl ester and/or indomethacin. To evaluate the role for AT1-R and AT2-R in Ang-II sensitivity, full concentration response curves were obtained for Ang-II in the presence of losartan or PD123319. mRNA expression of the AT1-R and AT2-R, eNOS and iNOS, COX1 and COX2 in aorta were evaluated using real-time RT-PCR.

Results: The role of vasodilator prostaglandins in the aorta was increased and the role of endothelium-derived hyperpolarizing factor and response of the AT1-R and AT2-R to Ang-II was decreased in pregnant saline infused rats as compared with non-pregnant rats. These changes were not observed during preeclampsia.

Conclusion: Pregnancy induced adaptations in endothelial function, which were not observed in the rat model for preeclampsia. This role of lack of pregnancy induced endothelial adaptation in the pathophysiology of experimental preeclampsia needs further investigation.

Original languageEnglish
Article numbere79884
Number of pages15
JournalPLoS ONE
Issue number11
Publication statusPublished - 6-Nov-2013


  • Angiotensin II
  • Angiotensin II Type 1 Receptor Blockers
  • Animals
  • Aorta
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Disease Models, Animal
  • Endothelial Cells
  • Female
  • Imidazoles
  • Lipopolysaccharides
  • Losartan
  • Nitric Oxide Synthase Type II
  • Pre-Eclampsia
  • Pregnancy
  • Prostaglandins
  • Pyridines
  • Rats
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Vasodilator Agents

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