Regulation of Sodium Balance and Blood Pressure by the AT 1A Receptor for Angiotensin II

Abstract —To examine the role of the angiotensin II (AT) 1A receptor in the regulation of blood pressure and sodium balance, we measured systolic blood pressure responses in AT 1A receptor–deficient ( Agtr1a −/−) and wild-type ( Agtr1a +/+) mice while dietary sodium content was systematically altered. On a 0.4% sodium diet, systolic blood pressures were significantly lower in Agtr1a −/− than in +/+ mice. In Agtr1a +/+ mice, changing dietary sodium content did not affect blood pressure. In contrast, when Agtr1a −/− mice were fed a high-salt diet (6% NaCl), their systolic blood pressures increased significantly from 79±4 to 94±4 mm Hg ( P Agtr1a −/− mice decreased further while on a low-salt diet from 82±3 to 69±3 mm Hg ( P Agtr1a +/+ and −/− mice. Although urinary sodium excretion was substantially reduced in both groups during the low-salt diet, cumulative sodium balances became negative in Agtr1a −/− mice despite a 6-fold increase in urinary aldosterone. We infer, therefore, that the reduced blood pressures in Agtr1a −/− mice on a normal diet are caused by depletion of sodium and extracellular volume. Their “sodium sensitivity” suggests a critical role for renal AT 1A receptors to modulate sodium handling.