Angiotensin II type 1 autoantibody induced hypertension during pregnancy is associated with renal endothelial dysfunction

Gend Med. 2011 Jun;8(3):184-8. doi: 10.1016/j.genm.2011.04.003. Epub 2011 May 20.

Abstract

Background: Previous investigations suggested that agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) might mediate a hypertensive response through dysregulation of the endothelin-1 system. AT1-AA induced hypertension was attenuated by the AT1 receptor and/or endothelin-1 type A receptor antagonists.

Objectives: This study was undertaken to determine if AT1-AA induced hypertension was associated with renal endothelial dysfunction.

Methods: We compared the vascular reactivity of renal interlobar arteries from normal pregnant control rats and AT1-AA long-term infused pregnant rats in the presence and absence of endothelin type A (ET(A)) receptor antagonism. Renal endothelial function was tested using isolated renal interlobar arteries in a pressure myograph, which were exposed to acetylcholine or sodium nitroprusside.

Results: Vasodilatory responses to the endothelial-dependent agonist acetylcholine were impaired in AT1-AA rats (74 [10]%) compared with normal pregnant controls (95 [5]%, P < 0.05). In the presence of ET(A) receptor antagonism, no differences were observed between controls or the AT1-AA treated group with regard to endothelial-dependent (acetylcholine) relaxation.

Conclusion: AT1-AA induced hypertension during pregnancy was associated with disparate renal endothelial responses to acetylcholine. The difference in renal vascular responses between AT1-AA and normal pregnant rats was abolished by ET(A) receptor blockade.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / immunology*
  • Disease Models, Animal
  • Endothelin A Receptor Antagonists
  • Endothelin-1 / immunology*
  • Female
  • Hypertension, Pregnancy-Induced / chemically induced
  • Hypertension, Pregnancy-Induced / immunology*
  • Hypertension, Renal / immunology*
  • Kidney
  • Pregnancy
  • Pregnancy, Animal / immunology*
  • Pyrrolidines
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / immunology*

Substances

  • Autoantibodies
  • Endothelin A Receptor Antagonists
  • Endothelin-1
  • Pyrrolidines
  • Receptor, Angiotensin, Type 1