Regulation of sodium balance and blood pressure by the AT(1A) receptor forangiotensin II

To examine the role of the angiotensin II (AT)(1A) receptor in the regulati on of blood pressure and sodium balance, we measured systolic blood pressur e 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 significantl y from 79+/-4 to 94+/-4 mm Hg (P<0.006). The low blood pressures of Agtr1a- /- mice decreased further while on a low-salt diet from 82+/-3 to 69+/-3 mm Hg (P<0.03). On the high-salt diet, urinary sodium excretion increased to similar levels in Agtr1a+/+ and -/- mice. Although urinary sodium excretion was substantially reduced in both groups during the low-salt diet, cumulat ive sodium balances became negative in Agtr1a-/- mice despite a 6-fold incr ease in urinary aldosterone. We infer, therefore, that the reduced blood pr essures in Agtr1a-/- mice on a normal diet are caused by depletion of sodiu m and extracellular volume. Their "sodium sensitivity" suggests a critical role for renal AT(1A) receptors to modulate sodium handling.