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(Hypertension. 2006;47:537.)
© 2006 American Heart Association, Inc.

Part 2 Original Articles

Renal Angiotensin Type 2 Receptors Mediate Natriuresis Via Angiotensin III in the Angiotensin II Type 1 Receptor–Blocked Rat

From the Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health System, Charlottesville.

Correspondence to Robert M. Carey, PO Box 801414, University of Virginia Health System, Charlottesville, VA 22908-1414. E-mail rmc4C{at}virginia.edu

Whereas angiotensin (Ang) II is the major effector peptide of the renin–angiotensin system, its metabolite, des-aspartyl¹-Ang II (Ang III), may also have biologic activity. We investigated the effects of renal interstitial (RI) administration of candesartan (CAND), a specific Ang II type 1 receptor (AT₁) blocker, with and without coinfusion of PD-123319 (PD), a specific Ang II type 2 receptor (AT₂) blocker, on Na⁺ excretion (U_NaV) in uninephrectomized rats. We also studied the effects of unilateral RI infusion of Ang II or Ang III on U_NaV with and without systemic infusion of CAND with the noninfused kidney as control. In rats receiving normal Na⁺ intake, RI CAND increased U_NaV from 0.07±0.08 to 0.82±0.17 µmol/min (P<0.01); this response was abolished by PD. During Na⁺ restriction, CAND increased U_NaV from 0.06±0.02 to 0.1±0.02 µmol/min (P<0.05); this response also was blocked by PD. In rats with both kidneys intact, in the absence of CAND, unilateral RI infusion of Ang III did not significantly alter U_NaV. However, with systemic CAND infusion, RI Ang III increased U_NaV from 0.08±0.01 µmol/min to 0.18±0.04 µmol/min (P<0.01) at 3.5 nmol/kg per minute, and U_NaV remained elevated throughout the infusion; this response was abolished by PD. However, RI infusion of Ang II did not significantly alter U_NaV at any infusion rate (3.5 to 80 nmol/kg per minute) with or without systemic CAND infusion. These results suggest that intrarenal AT₁ receptor blockade engenders natriuresis by activation of AT₂ receptors. AT₂ receptor activation via Ang III, but not via Ang II, mediates the natriuretic response in the presence of systemic AT₁ receptor blockade.

Key Words: angiotensin • sodium • natriuresis • angiotensin • receptors, angiotensin II

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