Effects Of AT₁ Receptor Autoantibodies From Preeclamptic Patients On Contractile Function Of Rat Vascular Ring

Background and Aim:Preeclampsia is the leading cause of maternal and fetal death,but its etiopathogenisis and pathogenesis are still unclear.In recent years,autoantibodies against angiotensinâ…¡AT₁ receptors (AT₁-AA)have been found in the sera of patients with preeclampsia.It can play an agonistic role in increasing intracellular Ca²⁺concentration,and induce oxidative stress and inflammatory reaction in placenta.It is well known that the main target of angiotensinâ…¡is vessel,however,the direct effect of AT₁-AA on blood vessel is unknown,and need to be determined.Methods:Collecting 30 blood samples from preeclamptic women and 30 cases from homogeneity normal pregnant women as control;synthesizing the antigenic peptide corresponding to the second extracellular loop of human angiotensinâ…¡AT₁ receptors(165-191).Detecting the titers of AT₁-AA from two groups by SA-ELISA;MAb Trap Kit for IgG extraction and purification; Using isolated rat aorta/microvascular ring to observe the effects of AT₁-AA on thoracic aorta, coronary artery and middle cerebral artery activities.Results:1.The titre and positive rate of AT₁-AA from preeclamptic patients remarkably increase:Compared with homogeneity normal pregnant women(21 qualified),the positive rate(8.3% vs.57.5%,p＜0.01)and titers of AT₁-AA from preeclamptic patients(26 qualified)were significant increased.2.AT₁-AA can increase the aortic vascular contractile tension: At the dose of 10^-6mol/L,AT₁-AA increased the peak systolic tension from the control of 1.02±0.04(g)to 1.72±0.17(g)(p＜0.01),no change was observed in control;Ang-â…¡showed similar increasing effects;and both of the increasing effects caused by AT₁-AA and Ang-â…¡could be blocked by 100 nmol/L Losartan(the blocker of AT₁-R).3.AT₁-AA can increase the coronary artery and middle cerebral artery contractile tension:At the dose of 10^-7mol/L,AT₁-AA increased the peak systolic tension of coronary artery and middle cerebral artery,which was higher than control.Effects could be blocked by 100nmol/L Losartan.Conclusion:1.Compared with control,titers and positive rate of AT₁-AA from preeclamptic patients were both increased.2.Just like angiotensinâ…¡,the AT₁-AA could dose-dependently increase the contractile tension of the aortic vascular ring,and the effects could be blocked by Losartan.These indicated that the effects of antibodies were induced by their stimulatory agonist-like activities on AT₁-receptors.3.The AT₁-AA could increase max contractile tension of coronary artery and middle cerebral artery,and would bring about receptor agonist-like activities.