Agonistic Autoantibodies to the Angiotensin II Type 1 Receptor Enhance ANG II Induced Renal Vascular Sensitivity and Reduce Renal Function during Pregnancy

摘要

Preeclamptic women produce agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA) and exhibit increased blood pressure (MAP), 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 ANGII. In this study MAP was elevated in all pregnant rats treated with ANG II with or without AT1-AA. Glomerular filtration rate (GFR) was reduced from 1.90 ±0.16 ml/min in normal pregnant (NP) to 1.20 ±0.08 in ANGII + AT1-AA rats. Renal blood flow (RBF) was decreased in ANGII + AT1-AA vs NP rats to 7.4 ±1.09 vs. 15.4 ±1.75 ml/min. Renal vascular resistance (RVR) was drastically increased between ANGII + AT1-AA vs NP rats (18.4 ±2.91 vs. 6.4 ±0.77 mmHg/ml/min). Isoprostane excretion was increased by a 3.5 fold in ANG II + AT1-AA vs. NP (1160±321 vs. 323±52 pg/ml). In conclusion ANG II and AT1-AA together, significantly decrease GFR by 37%, RBF by 50%, and caused a 3 fold increase in RVR and isoprostane levels vs 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.