Agonistic autoantibodies to the angiotensin II type 1 receptor enhance angiotensin II-induced renal vascular sensitivity and reduce renal function during pregnancy

Mark W. Cunningham, Jan M. Williams, Lorena Amaral, Nathan Usry, Gerd Wallukat, Ralf Dechend, Babbette Lamarca

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Preeclamptic women produce agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA) and exhibit increased blood pressure (mean arterial pressure), vascular sensitivity to angiotensin II (ANG II), and display a decrease in renal function. The objective of this study was to examine the renal hemodynamic changes during pregnancy in the presence of AT1-AAs with or without a slow pressor dose of ANG II. In this study, mean arterial pressure was elevated in all pregnant rats treated with ANG II with or without AT1-AA. Glomerular filtration rate was reduced from 1.90±0.16 mL/min in normal pregnant (NP) to 1.20±0.08 in ANG II+AT1-AA rats. Renal blood flow was decreased in ANG II+AT1-AA versus NP rats to 7.4±1.09 versus 15.4±1.75 mL/min. Renal vascular resistance was drastically increased between ANG II+AT1-AA versus NP rats (18.4±2.91 versus 6.4±0.77 mm Hg/mL per minute). Isoprostane excretion was increased by 3.5-fold in ANG II+AT1-AA versus NP (1160±321 versus 323±52 pg/mL). In conclusion, ANG II and AT1-AA together significantly decrease glomerular filtration rate by 37% and renal blood flow by 50% and caused a 3-fold increase in renal vascular resistance and isoprostane levels versus NP rats. These data indicate the importance of AT1-AAs to enhance ANG II-induced renal vasoconstriction and reduce renal function as mechanisms to cause hypertension as observed during preeclampsia.

Original languageEnglish
Pages (from-to)1308-1313
Number of pages6
JournalHypertension
Volume68
Issue number5
DOIs
StatePublished - 1 Nov 2016

Keywords

  • angiotensin II
  • autoantibodies
  • hypertension
  • preeclampsia
  • pregnancy

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