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Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor

Abstract

THERE are two major angiotensin II receptor isoforms, AT1 and AT2. AT1 mediates the well-known pressor and mitogenic effects of angiotensin II (refs 1-5), but the signalling mechanism and physiological role of AT2 (refs 6-11) has not been established. Its abundant expression in fetal tissues12 and certain brain nuclei13 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 haemo-dynamic effects, and that AT2 regulates central nervous system functions, including behaviour.

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Ichiki, T., Labosky, P., Shiota, C. et al. Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature 377, 748–750 (1995). https://doi.org/10.1038/377748a0

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