Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research, Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, QC, Canada.
J Renin Angiotensin Aldosterone Syst. 2010 Mar;11(1):19-31. doi: 10.1177/1470320309347785. Epub 2009 Oct 27.
Angiotensin II (Ang II) is considered the major final mediator of the renin-angiotensin system. The actions of Ang II have been implicated in many cardiovascular conditions, such as hypertension, atherosclerosis, coronary heart disease, restenosis, and heart failure. Ang II can act through two different receptors: Ang II type 1 (AT(1)) receptor and Ang II type 2 (AT(2)) receptor. The AT(1) receptor is ubiquitously expressed in the cardiovascular system and mediates most of the physiological and pathophysiological actions of Ang II. The AT(2) receptor is highly expressed in the developing foetus, but its expression is very low in the cardiovascular system of the normal adult. Expression of the AT(2) receptor can be modulated by pathological states associated with tissue remodelling or inflammation such as hypertension, atherosclerosis, and myocardial infarction. The precise role of the AT(2) receptor remains under debate. However, it appears that the AT(2) receptor plays a vasodilatory role, and may be enhanced as a countervailing mechanism in cardiac hypertrophy, and in presence of vascular injury in hypertension and atherosclerosis. Signalling pathways induced by the stimulation of the AT(2) receptor are poorly understood, but three main mechanisms have been described: (a) activation of protein phosphatases causing protein dephosphorylation; (b) activation of bradykinin/nitric oxide/cyclic guanosine 3',5'-monophosphate pathway; and (c) stimulation of phospholipase A(2) and release of arachidonic acid. Vasodilatory effects of the AT(2) receptor, probably the only well-established role of the AT(2) receptor, have been attributed to the second of these mechanisms. The participation of the AT(2) receptor in cardiovascular remodelling and inflammation is more controversial. In vitro, AT(2) receptor stimulation clearly inhibits cardiac and vascular smooth muscle growth and proliferation, and stimulates apoptosis. In vivo, the situation is less clear, and depending on the studies, the AT(2) receptor appears to be required for cardiac hypertrophic growth or contrariwise, the AT(2) receptor has demonstrated no effects on cardiac hypertrophy. Similar controversial findings have been reported in atherosclerosis. Here we discuss the role of the AT(2) receptor on cardiovascular structure and disease, and the signalling pathways induced by its activation.
血管紧张素 II（Ang II）被认为是肾素-血管紧张素系统的主要终末介质。Ang II 的作用与许多心血管疾病有关，如高血压、动脉粥样硬化、冠心病、再狭窄和心力衰竭。Ang II 可以通过两种不同的受体发挥作用：血管紧张素 II 型 1（AT(1)）受体和血管紧张素 II 型 2（AT(2)）受体。AT(1)受体在心血管系统中广泛表达，介导 Ang II 的大多数生理和病理生理作用。AT(2)受体在发育中的胎儿中高度表达，但在正常成人的心血管系统中表达水平很低。AT(2)受体的表达可以被与组织重塑或炎症相关的病理状态调节，如高血压、动脉粥样硬化和心肌梗死。AT(2)受体的确切作用仍存在争议。然而，似乎 AT(2)受体发挥血管舒张作用，并且可能在高血压和动脉粥样硬化中的血管损伤和心肌肥厚中作为一种代偿机制增强。刺激 AT(2)受体诱导的信号通路知之甚少，但已经描述了三种主要机制：（a）激活蛋白磷酸酶导致蛋白去磷酸化；（b）激活缓激肽/一氧化氮/环鸟苷 3'，5'-单磷酸途径；和（c）刺激磷脂酶 A(2)和释放花生四烯酸。AT(2)受体的血管舒张作用，可能是 AT(2)受体唯一得到充分证实的作用，归因于第二种机制。AT(2)受体在心血管重塑和炎症中的参与更具争议性。在体外，AT(2)受体刺激清楚地抑制心脏和血管平滑肌的生长和增殖，并刺激细胞凋亡。在体内，情况不太清楚，并且根据研究，AT(2)受体似乎是心脏肥厚生长所必需的，或者相反，AT(2)受体对心脏肥厚没有影响。在动脉粥样硬化中也报道了类似的有争议的发现。在这里，我们讨论 AT(2)受体在心血管结构和疾病中的作用，以及其激活诱导的信号通路。
