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Agonistic AT1 Receptor Autoantibody Increases in Serum of Patients with Refractory Hypertension and Improves Ca2+ Mobilization in Cultured Rat Vascular Smooth Muscle Cells

Abstract

Agonistic AT1 receptor autoantibodies (AT1-AAs) have been described in the patients with malignant hypertension or preeclampia. Furthermore, AT1-AAs were highly associated with refractory hypertension. Function of vascular smooth muscle cells (VSMCs) is important in the regulation of blood pressure. We investigated and compared the ability of angiotensin II (Ang II) and AT1-AAs to stimulate the intracellular calcium mobilization and cellular proliferation of rat VSMCs. Twenty-two patients with refractory hypertension, 24 patients with non-refractory hypertension and 37 normotensives were recruited. The serum of each patient was detected for the presence of AT1-AAs by ELISA. Ang II and the AT1-AAs from the sera of patients were used to stimulate rat VSMCs in vitro. AT1-AAs were detected in 10/22, 3/24 and 3/37 of patients with refractory hypertension, non-refractory hypertension and normotensives, respectively. AT1-AAs led the increase intracellular calcium mobilization in a dose-dependent manner and cellular proliferation of VSMCs just as Ang II. Both of these effects caused by AT1-AAs were blocked with losartan or a peptide corresponding to a part of the second extracellular loop of AT1 receptor. Since AT1-AAs exhibited pharmacological activity in rat VSMCs just as Ang II, they might play a role in the elevation of peripheral vascular resistance and in vascular remodeling. And AT1-AAs were suggested to involve in resistance to antihypertensive therapy.

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Correspondence to Yuhua Liao.

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Zhu, F., Sun, Y., Liao, Y. et al. Agonistic AT1 Receptor Autoantibody Increases in Serum of Patients with Refractory Hypertension and Improves Ca2+ Mobilization in Cultured Rat Vascular Smooth Muscle Cells. Cell Mol Immunol 5, 209–217 (2008). https://doi.org/10.1038/cmi.2008.26

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  • DOI: https://doi.org/10.1038/cmi.2008.26

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