Angiotensin Type-2 Receptors: Transducers of Natriuresis in the Renal Proximal Tubule

• Published in: International journal of molecular sciences Vol. 23; no. 4; p. 2317
• Main Authors: Carey, Robert M, Siragy, Helmy M, Gildea, John J, Keller, Susanna R
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19-02-2022; MDPI
• Subjects: Agonists; Amino acids; Aminopeptidase; Angiotensin; Angiotensin II; angiotensin receptor; Animals; Blood pressure; Bradykinin; Cyclic GMP; Hypertension; Kidneys; Metabolites; Microscopy; natriuresis; Nitric oxide; Peptides; Phosphoprotein phosphatase; Physiology; Protein phosphatase; Proteins; Reabsorption; renin-angiotensin system; Review; Sodium; sodium excretion; Stimulation; Transducers; blood pressure; natriuresis; angiotensin receptor; cyclic GMP; sodium excretion; protein phosphatase; renin-angiotensin system
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23042317

Angiotensin II (Ang II) type-2 receptors (AT
R) are expressed in the adult kidney, prominently in renal proximal tubule cells (RPTCs), and play an important role in opposing renal sodium (Na
) retention induced by Ang II stimulation of Ang II type-1 receptor (AT
R). Natriuresis induced by AT
R blockade is due at least in part to AT
R activation and whole body deletion of AT
Rs reduces the natriuretic response to increased blood pressure (BP). The major endogenous AT
R agonist mediating the natriuretic response is Ang III, the Ang II heptapeptide metabolite generated by aminopeptidase A, and the principal nephron site mediating inhibition of Na
reabsorption by the AT
R is the renal proximal tubule (RPT). AT
Rs induce natriuresis via a bradykinin, nitric oxide and cyclic GMP (cGMP) signaling cascade. Recent studies demonstrated a key role for protein phosphatase 2A (PP2A) in the AT
R-mediated natriuretic response upstream of cGMP. By inducing natriuresis, AT
Rs lower BP in the Ang II-infusion model of hypertension. PP2A activation and the natriuretic response to AT
R stimulation are defective in spontaneously hypertensive rats, a model of primary hypertension in humans. AT
R agonists are candidates for proximal tubule natriuretic agents in Na
and fluid retention disorders.