Autoantibody against AT1 receptor from preeclamptic patients induces vasoconstriction through angiotensin receptor activation.
2008
Abstract Preeclampsia is a serious pathologic complication during pregnancy, and its pathogenesis remains poorly understood. Recent studies have demonstrated that autoantibodies against angiotensin II type 1A receptor (AT1-AA) are present in women with preeclampsia. However, their role in the development of hypertension in preeclamptic patients has never been previously investigated. The present study was designed to determine whether AT1-AA isolated from the sera of preeclamptic patients causes vascular constriction and, if so, to further investigate the cellular receptors that mediate their vasoactivity. Blood samples were collected from 49 pregnant women (preeclampsia = 31, control = 18) and AT1-AA was detected using enzyme-linked immunosorbent assay. Vasoconstrictive effect of purified IgG from the sera of either preeclamptic patients or normal pregnant women was determined in isolated rat thoracic aorta, arteriae cerebri media and coronary artery. Compared with normal pregnant women, frequency of AT1-AA positive samples was markedly increased in preeclamptic patients (80.7 vs. 5.6%, P < 0.01). In isolated thoracic aortic rings, middle cerebral artery and coronary artery segments, AT1-AA induced vasoconstriction in a concentration-dependent fashion (P < 0.01). The vasoconstrictive effect of AT1-AA was completely blocked by losartan, an AT1-receptor antagonist. These data demonstrate that the AT1-AA causes significant vascular constriction in large conduit vessel as well as small resistant vessels though activation of the AT1 receptor. These results suggest that overproduction of AT1-AA is a novel risk factor in pregnant women and may play a causative role in the development of hypertension and vascular injury in preeclamptic patients.
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