Carey R M, Wang Z Q, Siragy H M
Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Hypertension. 2000 Jan;35(1 Pt 2):155-63. doi: 10.1161/01.hyp.35.1.155.
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.
肾素-血管紧张素系统是体液容量、电解质平衡和动脉血压的主要生理调节因子。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其对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）一直未知，这可能是因为与AT(1)受体相比，AT(2)受体的表达程度较低。现在已有证据表明，AT(2)受体与AT(1)受体介导的功能相反。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。这些生长反应的差异归因于不同的细胞信号通路，其中AT(1)受体刺激蛋白质磷酸化，而AT(2)受体使磷酸化去磷酸化。在过去5年中，研究表明AT(2)受体负责血管舒张和利钠作用，从而与通过AT(1)受体介导的ANG II的血管收缩和抗利钠作用相反。我们实验室和其他机构的研究表明，AT(2)受体通过包括缓激肽、一氧化氮和环鸟苷酸在内的自分泌级联反应刺激血管舒张和利钠作用。还发现AT(2)受体可控制血管舒张性前列腺素，其在血压调节中起作用。AT(2)受体似乎在血压和钠排泄调节中发挥一种与AT(1)受体相反的反调节保护作用。
