Angiotensin Type-2 Receptors: Transducers of Natriuresis in the Renal Proximal Tubule
Angiotensin II (Ang II) type-2 receptors (AT<sub>2</sub>R) are expressed in the adult kidney, prominently in renal proximal tubule cells (RPTCs), and play an important role in opposing renal sodium (Na<sup>+</sup>) retention induced by Ang II stimulation of Ang II type-1 rece...
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/2317 |
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| author | Robert M. Carey Helmy M. Siragy John J. Gildea Susanna R. Keller |
| author_facet | Robert M. Carey Helmy M. Siragy John J. Gildea Susanna R. Keller |
| author_sort | Robert M. Carey |
| collection | DOAJ |
| description | Angiotensin II (Ang II) type-2 receptors (AT<sub>2</sub>R) are expressed in the adult kidney, prominently in renal proximal tubule cells (RPTCs), and play an important role in opposing renal sodium (Na<sup>+</sup>) retention induced by Ang II stimulation of Ang II type-1 receptor (AT<sub>1</sub>R). Natriuresis induced by AT<sub>1</sub>R blockade is due at least in part to AT<sub>2</sub>R activation and whole body deletion of AT<sub>2</sub>Rs reduces the natriuretic response to increased blood pressure (BP). The major endogenous AT<sub>2</sub>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<sup>+</sup> reabsorption by the AT<sub>2</sub>R is the renal proximal tubule (RPT). AT<sub>2</sub>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<sub>2</sub>R-mediated natriuretic response upstream of cGMP. By inducing natriuresis, AT<sub>2</sub>Rs lower BP in the Ang II-infusion model of hypertension. PP2A activation and the natriuretic response to AT<sub>2</sub>R stimulation are defective in spontaneously hypertensive rats, a model of primary hypertension in humans. AT<sub>2</sub>R agonists are candidates for proximal tubule natriuretic agents in Na<sup>+</sup> and fluid retention disorders. |
| first_indexed | 2024-03-09T21:43:53Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:43:53Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-39dd546f47f441dea353a53ccd75cd6b2023-11-23T20:23:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234231710.3390/ijms23042317Angiotensin Type-2 Receptors: Transducers of Natriuresis in the Renal Proximal TubuleRobert M. Carey0Helmy M. Siragy1John J. Gildea2Susanna R. Keller3Division of Endocrinology and Metabolism, Department of Medicine University of Virginia Health System, Charlottesville, VA 22904, USADivision of Endocrinology and Metabolism, Department of Medicine University of Virginia Health System, Charlottesville, VA 22904, USADepartment of Pathology, University of Virginia Health System, Charlottesville, VA 22904, USADivision of Endocrinology and Metabolism, Department of Medicine University of Virginia Health System, Charlottesville, VA 22904, USAAngiotensin II (Ang II) type-2 receptors (AT<sub>2</sub>R) are expressed in the adult kidney, prominently in renal proximal tubule cells (RPTCs), and play an important role in opposing renal sodium (Na<sup>+</sup>) retention induced by Ang II stimulation of Ang II type-1 receptor (AT<sub>1</sub>R). Natriuresis induced by AT<sub>1</sub>R blockade is due at least in part to AT<sub>2</sub>R activation and whole body deletion of AT<sub>2</sub>Rs reduces the natriuretic response to increased blood pressure (BP). The major endogenous AT<sub>2</sub>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<sup>+</sup> reabsorption by the AT<sub>2</sub>R is the renal proximal tubule (RPT). AT<sub>2</sub>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<sub>2</sub>R-mediated natriuretic response upstream of cGMP. By inducing natriuresis, AT<sub>2</sub>Rs lower BP in the Ang II-infusion model of hypertension. PP2A activation and the natriuretic response to AT<sub>2</sub>R stimulation are defective in spontaneously hypertensive rats, a model of primary hypertension in humans. AT<sub>2</sub>R agonists are candidates for proximal tubule natriuretic agents in Na<sup>+</sup> and fluid retention disorders.https://www.mdpi.com/1422-0067/23/4/2317angiotensin receptorblood pressurenatriuresissodium excretionrenin-angiotensin systemcyclic GMP |
| spellingShingle | Robert M. Carey Helmy M. Siragy John J. Gildea Susanna R. Keller Angiotensin Type-2 Receptors: Transducers of Natriuresis in the Renal Proximal Tubule International Journal of Molecular Sciences angiotensin receptor blood pressure natriuresis sodium excretion renin-angiotensin system cyclic GMP |
| title | Angiotensin Type-2 Receptors: Transducers of Natriuresis in the Renal Proximal Tubule |
| title_full | Angiotensin Type-2 Receptors: Transducers of Natriuresis in the Renal Proximal Tubule |
| title_fullStr | Angiotensin Type-2 Receptors: Transducers of Natriuresis in the Renal Proximal Tubule |
| title_full_unstemmed | Angiotensin Type-2 Receptors: Transducers of Natriuresis in the Renal Proximal Tubule |
| title_short | Angiotensin Type-2 Receptors: Transducers of Natriuresis in the Renal Proximal Tubule |
| title_sort | angiotensin type 2 receptors transducers of natriuresis in the renal proximal tubule |
| topic | angiotensin receptor blood pressure natriuresis sodium excretion renin-angiotensin system cyclic GMP |
| url | https://www.mdpi.com/1422-0067/23/4/2317 |
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