Abstract 3543: Effects of Autoantibody against Angiotensin II AT1 Receptor on Cardiac activities of Rat and Transport across the Rat Placenta to the Fetal
Preeclampsia is a serious pregnancy-specific complication which threatens both mothers and their infants. Autoantibody against angiotensin (ANG) II AT1 receptor (AT1-AA) had been found in the sera of preeclamptic patients. However, the implicative role of the autoantibody in the pathogenesis of the disease is unclear. Current study explored the effects of AT1-AA on the cardiac performance in rat. AT1-AA significantly enhanced the cardiac function of isolated perfusing rat heart in a dose-dependent manner. AT1-AA increased the LVSP-LVDP, ±dp/dtmax from the control value of 7.20±1.41(kPa), 179.50±16.47 (kPa /s) and 76.01±12.76(kPa/s) to 9.75±2.34(kPa), 245.33±36.15(kPa /s) and 115.63±16.72(kPa /s) (all P<0.01). These effects of AT1-AA were almost identical with that of ANG II, and could been neutralized by losartan. To determine the mechanisms by which AT1-AA enhance the cardiac function, the effects of AT1-AA on ion channels were studied using whole cell patch clamp techniques. AT1-AA increased the ICa-L (PA/PF, 6.05±0.33 vs. 4.07±0.54, P<0.01), and decreased the Ik1 from the control of 2.36±0.23 to 0.78±0.43 (P<0.01). In addition, transport of AT1-AA from pregnant mater to fetus was observed. Six female rats were immunized with synthetic peptide corresponding to the sequences of the second extracellular loop of AT1 receptor fortnightly interval. On 8 weeks, the titres of AT1-AA increased significantly compared with control group (OD value, 2.76±0.08 vs. 0.43±0.05, P<0.01), then mated the immunized rats with normal male rats. The offsprings were found a high level of AT1-AA on 0 days (OD value, 1.21±0.28 vs. 0.08±0.01, compared with control group, P<0.01) and slightly decreased on 6 weeks (OD value, 0.58±0.03 vs. 0.24±0.04, P<0.01). In conclusion, current study indicated that AT1-AA induce cardiac positive inotropic effects through AT1 receptor by regulating ICa-L and Ik1 in myocardium, which suggested that AT1-AA may contribute to the cardiovascular dysfunction in preeclampsia. Furthermore, we concluded that AT1-AA can transport from mater to the fetal and indicated that the high level of AT1-AA in pregnant mother may play a physiopathologic role in fetus.