Endothelial cell activation in response to placental ischemia in pregnant rats is mediated by agonistic autoantibodies to the angiotensin type I receptor

Abstract

The release of soluble factors such as endothelin‐1 (ET‐1) and agonistic autoantibodies to the angiotensin II (AngII) type I receptor (AT1‐AA) may be important links between maternal endothelial cell activation and placental ischemia during hypertension in preeclamptic women. We recently demonstrated a role for AT1 receptor activation in mediating ET‐1 production by endothelial cells exposed to serum from pregnant rats with reductions in uterine perfusion pressure (RUPP). The purpose of this study was to determine if activation of the AT1 receptor on endothelial cells in response to placental ischemia is mediated by the AT1‐AA. To achieve this goal, HUVECs were exposed to RUPP serum in the presence and absence of a blocking peptide corresponding to the AT1AA binding site. Arterial pressure was significantly higher in RUPP rats (135+/−2mmHg)) than in normal pregnant rats (106+/−1mmHg). Six hours after exposure to control RUPP serum (n=14), the ET‐1 concentration in cell culture supernatant was 45.8+/− 7.2 pg/ml as compared to 25.0+/− 2.8 pg/ml from cell supernatant exposed to serum from normal pregnant rats (n=17). Interestingly, the increase in ET‐1 production in response to RUPP serum was abolished (20.5+/−3.0 pg/ml; n=17) by pretreatment with the AT1AA blocking peptide. These data indicate that the AT1AA mediates the increase in ET‐1 production induced by serum from pregnant rats exposed to placental ischemia.