on December 27, 2005
Published online before print December 27, 2005, doi: 10.1161/01.HYP.0000196950.48596.21
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Submitted on September 20, 2005
From the Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health System, Charlottesville. * To whom correspondence should be addressed. E-mail: rmc4C{at}virginia.edu.
Abstract--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 (UNaV) in uninephrectomized rats. We also studied the effects of unilateral RI infusion of Ang II or Ang III on UNaV with and without systemic infusion of CAND with the noninfused kidney as control. In rats receiving normal Na+ intake, RI CAND increased UNaV 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 UNaV 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 UNaV. However, with systemic CAND infusion, RI Ang III increased UNaV 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 UNaV remained elevated throughout the infusion; this response was abolished by PD. However, RI infusion of Ang II did not significantly alter UNaV 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.
Revised on October 21, 2005
Renal Angiotensin Type 2 Receptors Mediate Natriuresis Via Angiotensin III in the Angiotensin II Type 1 Receptor-Blocked Rat
Shetal H. Padia;
Key words: angiotensin • sodium • natriuresis • angiotensin • receptors, angiotensin II
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