Agonistic AT1 Receptor Autoantibody Increases in Serum of Patients with Refractory Hypertension and Improves Ca2+ Mobilization in Cultured Rat Vascular Smooth Muscle Cells
Agonistic AT1 Receptor Autoantibody Increases in Serum of Patients with Refractory Hypertension and Improves Ca2+ Mobilization in Cultured Rat Vascular Smooth Muscle Cells
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DOI：
10.1038/cmi.2008.26
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发表时间：
2008-06
影响因子：
24.1
通讯作者：
F. Zhu;Yan-xiang Sun;Yuhua Liao;Yumiao Wei;Ming Chen;Min Wang;Zihua Zhou
中科院分区：
文献类型：
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作者：
F. Zhu;Yan-xiang Sun;Yuhua Liao;Yumiao Wei;Ming Chen;Min Wang;Zihua Zhou
恶性高血压或先兆子痫患者中已描述了激动性 AT 1 受体自身抗体 (AT 1-AA)。此外，AT 1-AA 与难治性高血压高度相关。血管平滑肌细胞（VSMC）的功能对于血压调节很重要。我们研究并比较了血管紧张素 II (Ang II) 和 AT 1-AA 刺激大鼠 VSMC 细胞内钙动员和细胞增殖的能力。招募了 22 名难治性高血压患者、24 名非难治性高血压患者和 37 名血压正常患者。通过ELISA检测每位患者血清中AT 1-AA的存在。 Ang II 和患者血清中的 AT 1-AA 用于体外刺激大鼠 VSMC。在难治性高血压、非难治性高血压和血压正常的患者中，分别有 10/22、3/24 和 3/37 的患者检测到 AT 1-AA。 AT 1-AAs 与 Ang II 一样以剂量依赖性方式增加细胞内钙动员和 VSMC 细胞增殖。 AT 1-AA 引起的这两种效应均被氯沙坦或与 AT 1 受体第二细胞外环的一部分相对应的肽阻断。由于 AT 1-AA 在大鼠 VSMC 中表现出与 Ang II 一样的药理活性，因此它们可能在提高外周血管阻力和血管重塑中发挥作用。 AT 1-AA 被认为与抗高血压治疗的抵抗有关。
Agonistic AT 1 receptor autoantibodies (AT 1-AAs) have been described in the patients with malignant hypertension or preeclampia. Furthermore, AT 1-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 AT 1-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 AT 1-AAs by ELISA. Ang II and the AT 1-AAs from the sera of patients were used to stimulate rat VSMCs in vitro. AT 1-AAs were detected in 10/22, 3/24 and 3/37 of patients with refractory hypertension, non-refractory hypertension and normotensives, respectively. AT 1-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 AT 1-AAs were blocked with losartan or a peptide corresponding to a part of the second extracellular loop of AT 1 receptor. Since AT 1-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 AT 1-AAs were suggested to involve in resistance to antihypertensive therapy.