Role of the angiotensin type 2 receptor in the regulation of blood pressure and renal function
Role of the angiotensin type 2 receptor in the regulation of blood pressure and renal function
复制标题
DOI：
10.1161/01.hyp.35.1.155
复制
发表时间：
2000-01-01
期刊：
影响因子：
8.3
通讯作者：
Siragy, HM
中科院分区：
文献类型：
--
作者：
Carey, RM;Wang, ZQ;Siragy, HM
肾素-血管紧张素系统是体液容量、电解质平衡和动脉压的主要生理调节剂。几乎所有主要效应肽血管紧张素II（ANG II）的生物学作用都归因于对1型（AT（1））ANG受体的作用。直到最近，2型（AT（2））受体的功能作用（如果有的话）一直是未知的，这可能是因为AT（2）受体与AT（1）受体相比具有低程度的表达。现在已经积累的证据表明，AT（2）受体对抗AT（1）受体介导的功能。AT（1）受体刺激细胞增殖，而AT（2）受体抑制增殖并促进细胞分化。生长反应的这些差异归因于不同的细胞信号传导途径，其中AT（1）受体刺激蛋白磷酸化和AT（2）受体去磷酸化。在过去的5年中，研究表明AT（2）受体负责血管舒张和尿钠排泄，从而对抗AT（1）受体介导的ANG II的血管收缩和抗利尿作用。我们实验室和其他人的工作表明，AT（2）受体通过包括缓激肽、一氧化氮和环GMP的自分泌级联反应刺激血管舒张和尿钠排泄。AT（2）受体也被发现控制血管扩张剂肾上腺素，肾上腺素在血压调节中起作用。AT（2）受体似乎在调节血压和钠排泄方面发挥反调节保护作用，与AT（1）受体相反。
The renin-angiotensin system is a major physiological regulator of body fluid volume, electrolyte balance, and arterial pressure. Virtually all of the biological actions of the principle effector peptide angiotensin II (ANG II) have been attributed to an action at the type 1 (AT(1)) ANG receptor. Until recently, the functional role of the type 2 (AT(2)) receptor, if any, has been unknown, possibly because the AT(2) receptor has a low degree of expression compared with that of the AT(1) receptor. Evidence has now accumulated that the AT(2) receptor opposes functions mediated by the AT(1) receptor. Whereas the AT(1) receptor stimulates cell proliferation, the AT(2) receptor inhibits proliferation and promotes cell differentiation. These differences in growth responses have been ascribed to different cell signaling pathways in which the AT(1) receptor stimulates protein phosphorylation and the AT(2) receptor dephosphorylation. During the past 5 years, studies have demonstrated that the AT(2) receptor is responsible for vasodilation and natriuresis, thus opposing the vasoconstrictor and antinatriuretic effects of ANG II mediated through the AT(1) receptor, Work from our laboratory and others indicates that the AT(2) receptor stimulates vasodilation and natriuresis by an autocrine cascade including bradykinin, nitric oxide, and cyclic GMP. The AT(2) receptor also has been found to control vasodilator prostaglandins, which have a role in blood pressure regulation. The AT(2) receptor appears to play a counterregulatory protective role in the regulation of blood pressure and sodium excretion that opposes the AT(1) receptor.