BEHAVIORAL AND CARDIOVASCULAR EFFECTS OF DISRUPTING THE ANGIOTENSIN-II TYPE-2 RECEPTOR GENE IN MICE

ANGIOTENSIN II, a potent regulator of blood pressure and of water and electrolyte balance, binds to two different G-protein-coupled receptors. The type-1 receptor (AT(1)) mediates the vasopressive and aldosterone-secreting effects of angiotensin II, but the function of the type-2 receptor (AT(2); refs 1, 2) is unknown, although it is expressed in both adult(3) and embryonic(4) life. To address this question, we have generated mice lacking the gene encoding the AT(2) receptor. Mutant mice develop normally, but have an impaired drinking response to water deprivatian as well as a reduction in spontaneous movements. Their baseline blood pressure is normal, but they show an increased vasopressor response to injection of angiotensin II. Thus, although the AT(2) receptor is not required for embryonic development, it plays a role in the central nervous system and cardiovascular functions that are mediated by the renin-angiotensin system.