Ardaillou R, Chansel D
INSERM 64, Hôpital Tenon, Paris, France.
J Hypertens Suppl. 1993 Apr;11(3):S43-7.
To examine the glomerular effects of angiotensin II (Ang II).
A survey of recent studies that have provided relevant information.
Glomeruli and mesangial cells of murine and human origin have receptors for Ang II (AT receptors) that are linked to phospholipase C. The dissociation constant (Kd) for these receptors is in the nanomolar range, and they are denser in freshly isolated glomeruli than in cultured mesangial cells. Pharmacological studies with the AT1 receptor, using losartan and its metabolite E3174, and with the AT2 receptor using PD 123177 and CGP 42112A, have shown that glomerular receptors for Ang II belong to the AT1 type. Furthermore, all the functional effects of Ang II in glomeruli and mesangial cells, including a rise in intracellular calcium, the stimulation of prostaglandin and protein synthesis, and glomerular vasoreactivity, are mediated by the AT1 receptor. [3H]-losartan binds specifically to mesangial cells but with different parameters from those observed for [125I]-Ang II. Losartan and E 3174 behave as non-competitive antagonists. Losartan exhibits some intrinsic effects but only at high concentrations not likely to be reached in vivo at normal doses. AT1 receptors in glomeruli are downregulated by plasma concentrations of Ang II and losartan.
These results demonstrate that the cellular mode of action of Ang II in glomeruli is mediated by the AT1 receptor type.
研究血管紧张素II（Ang II）对肾小球的影响。
对近期提供相关信息的研究进行综述。
源自小鼠和人类的肾小球及系膜细胞具有与磷脂酶C相连的Ang II受体（AT受体）。这些受体的解离常数（Kd）处于纳摩尔范围，且在新鲜分离的肾小球中比在培养的系膜细胞中更密集。使用氯沙坦及其代谢产物E3174对AT1受体进行的药理学研究，以及使用PD 123177和CGP 42112A对AT2受体进行的药理学研究表明，Ang II的肾小球受体属于AT1型。此外，Ang II在肾小球和系膜细胞中的所有功能作用，包括细胞内钙升高、前列腺素和蛋白质合成的刺激以及肾小球血管反应性，均由AT1受体介导。[3H] - 氯沙坦特异性结合系膜细胞，但参数与[125I] - Ang II观察到的不同。氯沙坦和E 3174表现为非竞争性拮抗剂。氯沙坦表现出一些内在作用，但仅在正常剂量下体内不太可能达到的高浓度时才会出现。肾小球中的AT1受体被血浆中的Ang II和氯沙坦下调。
这些结果表明，Ang II在肾小球中的细胞作用模式由AT1受体类型介导。
