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

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.