Intrarenal Angiotensin III Is the Predominant Agonist for Proximal Tubule Angiotensin Type 2 Receptors
Open Access
- 1 August 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 60 (2), 387-395
- https://doi.org/10.1161/HYPERTENSIONAHA.112.191403
Abstract
In angiotensin type 1 receptor–blocked rats, renal interstitial (RI) administration of des-aspartyl 1 -angiotensin II (Ang III) but not angiotensin II induces natriuresis via activation of angiotensin type 2 receptors. In the present study, renal function was documented during systemic angiotensin type 1 receptor blockade with candesartan in Sprague-Dawley rats receiving unilateral RI infusion of Ang III. Ang III increased urine sodium excretion, fractional sodium, and lithium excretion. RI coinfusion of specific angiotensin type 2 receptor antagonist PD-123319 abolished Ang III–induced natriuresis. The natriuretic response observed with RI Ang III was not reproducible with RI angiotensin (1-7) alone or together with angiotensin-converting enzyme inhibition. Similarly, neither RI angiotensin II alone or in the presence of aminopeptidase A inhibitor increased urine sodium excretion. In the absence of systemic angiotensin type 1 receptor blockade, Ang III alone did not increase urine sodium excretion, but natriuresis was enabled by the coinfusion of aminopeptidase N inhibitor and subsequently blocked by PD-123319. In angiotensin type 1 receptor–blocked rats, RI administration of aminopeptidase N inhibitor alone also induced natriuresis that was abolished by PD-123319. Ang III–induced natriuresis was accompanied by increased RI cGMP levels and was abolished by inhibition of soluble guanylyl cyclase. RI and renal tissue Ang III levels increased in response to Ang III infusion and were augmented by aminopeptidase N inhibition. These data demonstrate that endogenous intrarenal Ang III but not angiotensin II or angiotensin (1-7) induces natriuresis via activation of angiotensin type 2 receptors in the proximal tubule via a cGMP–dependent mechanism and suggest aminopeptidase N inhibition as a potential therapeutic target in hypertension.Keywords
This publication has 24 references indexed in Scilit:
- Relative affinity of angiotensin peptides and novel ligands at AT1 and AT2 receptorsClinical Science, 2011
- Angiotensin III Stimulates Aldosterone Secretion from Adrenal Gland Partially via Angiotensin II Type 2 Receptor But Not Angiotensin II Type 1 ReceptorEndocrinology, 2011
- Angiotensin II AT2receptors inhibit proximal tubular Na+-K+-ATPase activity via a NO/cGMP-dependent pathwayAmerican Journal of Physiology-Renal Physiology, 2006
- Renal Angiotensin Type 2 Receptors Mediate Natriuresis Via Angiotensin III in the Angiotensin II Type 1 Receptor–Blocked RatHypertension, 2006
- Newly Recognized Components of the Renin-Angiotensin System: Potential Roles in Cardiovascular and Renal RegulationEndocrine Reviews, 2003
- Pathways for angiotensin-(1—7) metabolism in pulmonary and renal tissuesAmerican Journal of Physiology-Renal Physiology, 2000
- Distribution of angiotensin AT1and AT2receptor subtypes in the rat kidneyAmerican Journal of Physiology-Renal Physiology, 1999
- Kidney Aminopeptidase A and Hypertension, Part IIHypertension, 1999
- Expression of the Subtype 2 Angiotensin (AT 2 ) Receptor Protein in Rat KidneyHypertension, 1997
- The Validity of Lithium Clearance as an Index of Sodium and Water Delivery from the Proximal TubulesNephron, 1997