title: 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<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, 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.
authors.affiliation: Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705, USA.
authors.forename: M I
authors.initials: MI
authors.lastname: Oliverio
authors.forename: C F
authors.initials: CF
authors.lastname: Best
authors.forename: O
authors.initials: O
authors.lastname: Smithies
authors.forename: T M
authors.initials: TM
authors.lastname: Coffman
mesh_terms: D000450:Aldosterone / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics / Q000502:physiology*; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000008:administration & dosage*; D013599:Systole
chemical_list: D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D000450:Aldosterone; D012964:Sodium