Ichiki T, Labosky P A, Shiota C, Okuyama S, Imagawa Y, Fogo A, Niimura F, Ichikawa I, Hogan B L, Inagami T
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville 37232, USA.
Nature. 1995 Oct 26;377(6551):748-50. doi: 10.1038/377748a0.
There are two major angiotensin II receptor isoforms, AT1 and AT2. AT1 mediates the well-known pressor and mitogenic effects of angiotensin II, but the signalling mechanism and physiological role of AT2 has not been established. Its abundant expression in fetal tissues and certain brain nuclei suggest possible roles in growth, development and neuronal functions. Here we report the unexpected finding that the targeted disruption of the mouse AT2 gene resulted in a significant increase in blood pressure and increased sensitivity to the pressor action of angiotensin II. Thus AT2 mediates a depressor effect and antagonizes the AT1-mediated pressor action of angiotensin II. In addition, disruption of the AT2 gene attenuated exploratory behaviour and lowered body temperature. Our results show that angiotensin II activates AT1 and AT2, which have mutually counteracting haemodynamic effects, and that AT2 regulates central nervous system functions, including behaviour.
有两种主要的血管紧张素II受体亚型，即AT1和AT2。AT1介导血管紧张素II众所周知的升压和促有丝分裂作用，但AT2的信号传导机制和生理作用尚未明确。它在胎儿组织和某些脑核中的大量表达表明其在生长、发育和神经元功能中可能发挥作用。在此我们报告了一个意外发现，即小鼠AT2基因的靶向破坏导致血压显著升高，并增加了对血管紧张素II升压作用的敏感性。因此，AT2介导降压作用，并拮抗AT1介导的血管紧张素II升压作用。此外，AT2基因的破坏减弱了探索行为并降低了体温。我们的结果表明，血管紧张素II激活AT1和AT2，它们具有相互抵消的血流动力学效应，并且AT2调节包括行为在内的中枢神经系统功能。
