Why do we need a selective angiotensin II type 2 receptor agonist?
Why do we need a selective angiotensin II type 2 receptor agonist?
复制标题
为什么我们需要选择性血管紧张素 II 2 型受体激动剂？
作者：
D. Henrion
参见相关文章，第722-729页
肾素-血管紧张素系统在血压和水平衡的调节中具有核心作用。它也是治疗高血压的主要靶点。血管紧张素II有2种主要受体，1型受体（AT 1 R）和2型受体（AT 2 R），两者都与G蛋白偶联。在心血管疾病中观察到的不良血管重构归因于AT 1 R，并且现在大量相对选择性的AT 1 R抑制剂用于患者。AT 2 R的作用通常表现为抵消AT 1 R的作用。因此，AT 1 R阻滞剂（血管紧张素受体阻滞剂）的一些有益作用通常归因于AT 2 R激活。1 AT 2 R的有益血管作用现已被多项研究证明。例如，AT 2 R刺激可降低血管紧张素II和AT 1 R拮抗剂缬沙坦处理的血管平滑肌细胞中血管RhoA/Rho激酶/肌球蛋白轻链磷酸化，以及坎地沙坦慢性处理的自发性高血压大鼠的主动脉中的血管RhoA/Rho激酶/肌球蛋白轻链磷酸化。2总之，既往研究表明血管AT 2 R在慢性AT 1 R阻断期间的血压降低中发挥作用。类似地，在高血压糖尿病患者中，长期血管紧张素受体阻滞剂治疗增加了AT 2 R表达水平和肠系膜阻力动脉的AT 2 R依赖性血管舒张。3然而，在缺乏AT 1 R抑制的情况下，AT 2 R的表达在生理和病理生理条件下变化很大，拮抗剂PD 123319的选择性相对较低，激动剂CGP 42112的特异性较弱，这无助于充分理解其作用。
See related article, pp 722–729
The renin-angiotensin system has a central role in the regulation of blood pressure and water balance. It is also a main target in the treatment of hypertension. Angiotensin II has 2 major receptors, the type 1 (AT1R) and the type 2 receptor (AT2R), both coupled to G proteins. Adverse vascular remodeling observed in cardiovascular diseases is attributed to AT1R, and a large number of relatively selective AT1R inhibitors are now used in patients. The effects of AT2R are usually presented as counteracting the effects exerted by AT1R. Consequently, some beneficial effects of the AT1R blockers (angiotensin receptor blocker) are commonly attributed to AT2R activation.1 Beneficial vascular effects of AT2R have now been proven by several studies. For example, AT2R stimulation reduces vascular RhoA/Rho kinase/myosin light chain phosphorylation in angiotensin II and AT1R antagonist valsartan-treated vascular smooth muscle cells in vitro, as well as in the aorta of spontaneously hypertensive rats chronically treated with candesartan.2 Altogether, previous studies suggest a role for vascular AT2R in blood pressure lowering during chronic AT1R blockade. Similarly, in hypertensive diabetic patients, chronic angiotensin receptor blocker treatment increases AT2R expression level and AT2R-dependent vasodilatation of mesenteric resistance arteries.3 Nevertheless, in the absence of AT1R inhibition, expression of AT2R varies a lot under physiological and pathophysiological conditions,4 and the relatively low selectivity of the antagonist PD123319 and the weak specificity of the agonist CGP42112 do not help fully understand the role …
影响因子：
5.5
作者：
Lee, Seong-Ki;Boron, Walter F.;Parker, Mark D.
通讯作者：
Parker, Mark D.