Regulation of sodium balance and blood pressure by the AT(1A) receptor for angiotensin II.
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.
Oliverio
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Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705, USA.
Best
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Smithies
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Coffman
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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
D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D000450:Aldosterone; D012964:Sodium