Renal Angiotensin Type 2 Receptors Mediate Natriuresis Via Angiotensin III in the Angiotensin II Type 1 Receptor–Blocked Rat
- 1 March 2006
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 47 (3), 537-544
- https://doi.org/10.1161/01.hyp.0000196950.48596.21
Abstract
Whereas angiotensin (Ang) II is the major effector peptide of the renin–angiotensin system, its metabolite, des-aspartyl 1 -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 (AT 1 ) blocker, with and without coinfusion of PD-123319 (PD), a specific Ang II type 2 receptor (AT 2 ) blocker, on Na + excretion (U Na V) in uninephrectomized rats. We also studied the effects of unilateral RI infusion of Ang II or Ang III on U Na V with and without systemic infusion of CAND with the noninfused kidney as control. In rats receiving normal Na + intake, RI CAND increased U Na V from 0.07±0.08 to 0.82±0.17 μmol/min ( P + restriction, CAND increased U Na V from 0.06±0.02 to 0.1±0.02 μmol/min ( P Na V. However, with systemic CAND infusion, RI Ang III increased U Na V from 0.08±0.01 μmol/min to 0.18±0.04 μmol/min ( P Na V remained elevated throughout the infusion; this response was abolished by PD. However, RI infusion of Ang II did not significantly alter U Na V at any infusion rate (3.5 to 80 nmol/kg per minute) with or without systemic CAND infusion. These results suggest that intrarenal AT 1 receptor blockade engenders natriuresis by activation of AT 2 receptors. AT 2 receptor activation via Ang III, but not via Ang II, mediates the natriuretic response in the presence of systemic AT 1 receptor blockade.Keywords
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