ArticleCirculation research2016
AT2 Receptor Activation Prevents Sodium Retention and Reduces Blood Pressure in Angiotensin II-Dependent Hypertension.
Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Protein phosphatase 2A subunit B55 alpha is required for angiotensin type 2 receptor elicited natriuresis.American journal of physiology. Renal physiology · 2026Article
- The relationship between estrogen and renin angiotensin system components in the context of hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Review
- Polyphenolic Compounds in the Prevention and Treatment of Hypertension: A Review.International journal of molecular sciences · 2025Review
- Novel Antihypertensive Medications to Target the Renin-Angiotensin System: Mechanisms and Research.Reviews in cardiovascular medicine · 2025Review
- Enhancing glymphatic transport through angiotensin II type 2 receptor activation promotes neurological recovery after traumatic brain injury.Theranostics · 2025Article
- Nitric oxide-cyclic GMP role in Ang II induced hyperpolarization in bovine aortic endothelium cell line (BAE-1).Cytotechnology · 2024Article
- Intracellular Angiotensin II Stimulation of Sodium Transporter Expression in Proximal Tubule Cells via ATCells · 2023Article
- Pathogenesis of Chronic Kidney Disease Is Closely Bound up with Alzheimer's Disease, Especially via the Renin-Angiotensin System.Journal of clinical medicine · 2023Review
- Counter-regulatory renin-angiotensin system in hypertension: Review and update in the era of COVID-19 pandemic.Biochemical pharmacology · 2023Review
- Sex differences in the renin-angiotensin-aldosterone system and its roles in hypertension, cardiovascular, and kidney diseases.Frontiers in cardiovascular medicine · 2023Review
- The Angiotensin ATPharmacological reviews · 2022Review
- Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting.Pharmacological reviews · 2022Review
- G-protein-coupled receptor kinase 4 causes renal angiotensin II type 2 receptor dysfunction by increasing its phosphorylation.Clinical science (London, England : 1979) · 2022Article
- Angiotensin II type-2-receptor stimulation ameliorates focal and segmental glomerulosclerosis in mice.Clinical science (London, England : 1979) · 2022Article
- Angiotensin II and ATInternational journal of molecular sciences · 2022Review
- Angiotensin Type-2 Receptors: Transducers of Natriuresis in the Renal Proximal Tubule.International journal of molecular sciences · 2022Review
- Renal ATCirculation research · 2022Article
- The NaFrontiers in physiology · 2022Review
- Amelioration of Hypertension by Oryeongsan through Improvements of Body Fluid and Sodium Balance: Roles of the Renin-Angiotensin System and Atrial Natriuretic Peptide System.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Role of the Renin-Angiotensin-Aldosterone and Kinin-Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID.International journal of molecular sciences · 2021Review
Corrections and comments
- Commented on by
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleCompound 21 (C-21) is a highly selective nonpeptide angiotensin AT2 receptor (AT2R) agonist.
objectiveTo test the hypothesis that chronic AT2R activation with C-21 induces natriuresis via an action at the renal proximal tubule (RPT) and lowers blood pressure (BP) in experimental angiotensin II (Ang II)-dependent hypertension. METHODS AND
resultsIn rats, Ang II infusion increased both sodium (Na(+)) retention and BP on day 1, and BP remained elevated throughout the 7-day infusion period. Either intrarenal or systemic administration of C-21 prevented Ang II-mediated Na(+) retention on day 1, induced continuously negative cumulative Na(+) balance compared with Ang II alone, and reduced BP chronically. The effects of C-21 are likely to be mediated by action on the RPT as acute systemic C-21-induced natriuresis was additive to that induced by chlorothiazide and amiloride. At 24 hours of Ang II infusion, AT2R activation with C-21, both intrarenally and systemically, translocated AT2Rs from intracellular sites to the apical plasma membranes of RPT cells without altering the total cellular pool of AT2Rs and internalized/inactivated major RPT Na(+) transporters Na(+)-H(+)-exchanger-3 and Na(+)/K(+)ATPase. C-21 lowered BP to a similar degree whether administered before or subsequent to the establishment of Ang II-dependent hypertension.
conclusionsChronic AT2R activation initiates and sustains receptor translocation to RPT apical plasma membranes, internalizes/inactivates Na(+)-H(+)-exchanger-3 and Na(+)/K(+)ATPase, prevents Na(+) retention resulting in negative cumulative Na(+) balance, and lowers BP in experimental Ang II-induced hypertension. Acting uniquely at the RPT, C-21 is a promising candidate for the treatment of hypertension and Na(+)-retaining states in humans.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.