Pressor and Renal Hemodynamic Effects of the Novel Angiotensin A Peptide Are Angiotensin II Type 1A Receptor Dependent
Pressor and Renal Hemodynamic Effects of the Novel Angiotensin A Peptide Are Angiotensin II Type 1A Receptor Dependent
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新型血管紧张素 A 肽的升压和肾血流动力学效应依赖于血管紧张素 II 1A 型受体
DOI：
10.1161/hypertensionaha.110.161836
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发表时间：
2011
期刊：
影响因子：
8.3
通讯作者：
A. Dupont
中科院分区：
文献类型：
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作者：
Rui Yang;I. Smolders;P. Vanderheyden;H. Demaegdt;A. Van Eeckhaut;G. Vauquelin;Aneta Lukaszuk;D. Tourwé;S. Chai;A. Albiston;C. Nahmias;T. Walther;A. Dupont
最近，人们发现健康人的血浆中存在一种新的血管紧张素 (Ang) II 衍生物，称为“Ang A”，并且在终末期肾衰竭患者中的浓度有所增加。该研究的目的是研究正常血压和高血压大鼠以及转基因小鼠的血压和肾血流动力学对 Ang A 的反应，以及 Ang A 与 Ang II 1 型 (AT1) 或 Ang II 2 型 (AT2) 受体的结合特性。静脉内和肾内给予 Ang A 在血压正常的大鼠中诱导剂量依赖性升压和肾血管收缩反应，该反应被 AT1 受体拮抗剂坎地沙坦阻断，但不被 AT2 受体配体 PD123319、CGP42112A 或化合物 21 改变。在自发性高血压大鼠中静脉注射后观察到类似的反应。小鼠体内 AT1a 受体的缺失几乎完全消除了对 Ang A 的升压和肾血管收缩反应，表明其作用是通过 AT1a 受体介导的。 Ang A 在体内的效力低于 Ang II。体外研究表明，Ang A 是 AT1 受体的完全激动剂，对 AT1 和 AT2 受体的亲和力与 Ang II 相似。总体而言，对 Ang A 和 Ang II 的反应相似。 Ang A 没有调节 Ang II 的升压和肾血流动力学效应的生理作用。
Recently, a new derivative of angiotensin (Ang) II, called “Ang A,” has been discovered to be present in plasma of healthy humans and, in increased concentrations, in end-stage renal failure patients. The objectives of the study were to investigate the blood pressure and renal hemodynamic responses to Ang A in normotensive and hypertensive rats and in genetically modified mice and the binding properties of Ang A to Ang II type 1 (AT1) or Ang II type 2 (AT2) receptors. Intravenous and intrarenal administration of Ang A induced dose-dependent pressor and renal vasoconstrictor responses in normotensive rats, which were blocked by the AT1 receptor antagonist candesartan but were not altered by the AT2 receptor ligands PD123319, CGP42112A, or compound 21. Similar responses were observed after intravenous administration in spontaneously hypertensive rats. Deletion of AT1a receptors in mice almost completely abolished the pressor and renal vasoconstrictor responses to Ang A, indicating that its effects are mediated via AT1a receptors. Ang A was less potent than Ang II in vivo. The in vitro study demonstrated that Ang A is a full agonist for AT1 receptors, with similar affinity for AT1 and AT2 receptors as Ang II. Overall, the responses to Ang A and Ang II were similar. Ang A has no physiological role to modulate the pressor and renal hemodynamic effects of Ang II.
影响因子：
3.1
作者：
Masami Tanaka;Shinya Tsuchida;T. Imai;N. Fujii;Hitoshi Miyazaki;Toshihiro Ichiki;Mitsuhide Naruse;Tadashi Inagami
通讯作者：
Masami Tanaka;Shinya Tsuchida;T. Imai;N. Fujii;Hitoshi Miyazaki;Toshihiro Ichiki;Mitsuhide Naruse;Tadashi Inagami
影响因子：
21.1
作者：
M. Gasparo;K. Catt;T. Inagami;J. Wright;T. Unger
通讯作者：
M. Gasparo;K. Catt;T. Inagami;J. Wright;T. Unger