EFFECTS ON BLOOD-PRESSURE AND EXPLORATORY-BEHAVIOR OF MICE LACKING ANGIOTENSIN-II TYPE-2 RECEPTOR

THERE are two major angiotensin II receptor isoforms, AT(1) and AT(2). AT(1) mediates the well-known presser and mitogenic effects of angiot ensin II (refs 1-5), but the signalling mechanism and physiological ro le of AT(2) (refs 6-11) has not been established. Its abundant express ion in fetal tissues(12) and certain brain nuclei(13) suggest possible roles in growth, development and neuronal functions. Here we report t he unexpected finding that the targeted disruption of the mouse AT(2) gene resulted in a significant increase in blood pressure and increase d sensitivity to the presser action of angiotensin II. Thus AT(2) medi ates a depressor effect and antagonizes the AT(1)-mediated presser act ion of angiotensin II. In addition, disruption of the AT(2) gene atten uated exploratory behaviour and lowered body temperature. Our results show that angiotensin II activates AT(1) and AT(2), which have mutuall y counteracting haemodynamic effects, and that AT(2) regulates central nervous system functions, including behaviour.