ArticleCirculation research2014
AT₂ receptor activation induces natriuresis and lowers blood pressure.
Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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74 citing papers in PubMed, 114 citations in OpenAlex.
- AT2R activation reduces M1-type macrophages and promotes tregs accumulation in ischemia-reperfusion-induced acute kidney injury.Frontiers in pharmacology · 2026Article
- Protein phosphatase 2A subunit B55 alpha is required for angiotensin type 2 receptor elicited natriuresis.American journal of physiology. Renal physiology · 2026Article
- GPCRs identified on mitochondrial membranes: New therapeutic targets for diseases.Journal of pharmaceutical analysis · 2025Review
- Novel Antihypertensive Medications to Target the Renin-Angiotensin System: Mechanisms and Research.Reviews in cardiovascular medicine · 2025Review
- The Balance Between the Natriuretic Peptides and the Renin-Angiotensin-Aldosterone System in the Preservation of Ideal Cardiovascular Health.Journal of clinical medicine · 2025Review
- Deletion of ATAmerican journal of physiology. Renal physiology · 2024Article
- Herbal medicine Oryeongsan (Wulingsan): Cardio-renal effects via modulation of renin-angiotensin system and atrial natriuretic peptide system.Integrative medicine research · 2024Review
- Herbal medicine (Oryeongsan) for fluid and sodium balance in renal cortex of spontaneously hypertensive rats.Integrative medicine research · 2024Article
- Angiotensin-II type 2 receptor-mediated renoprotection is independent of receptor Mas in obese Zucker rats fed high-sodium diet.Frontiers in pharmacology · 2024Article
- Eukaryotic elongation factor 2 kinase inhibitor, A484954 induced diuresis via nitric oxide production in spontaneously hypertensive rats.The Journal of veterinary medical science · 2023Article
- Restoring Angiotensin Type 2 Receptor Function Reverses PFOS-Induced Vascular Hyper-Reactivity and Hypertension in Pregnancy.International journal of molecular sciences · 2023Article
- Stimulation of angiotensin II type 2 receptor attenuates organ injury in rats with polymicrobial sepsis.Journal of the Chinese Medical Association : JCMA · 2023Article
- Intracellular Angiotensin II Stimulation of Sodium Transporter Expression in Proximal Tubule Cells via ATCells · 2023Article
- Angiotensin II type 2 receptor activation preserves megalin in the kidney and prevents proteinuria in high salt diet fed rats.Scientific reports · 2023Article
- Effect of DCardiology discovery · 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
- Characterization of the First Animal Toxin Acting as an Antagonist on AT1 Receptor.International journal of molecular sciences · 2023Article
- Crosstalk between the renin-angiotensin, complement and kallikrein-kinin systems in inflammation.Nature reviews. Immunology · 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
14 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleCompound 21 (C-21) is a highly selective nonpeptide AT2 receptor (AT2R) agonist.
objectiveTo test the hypothesis that renal proximal tubule AT2Rs induce natriuresis and lower blood pressure in Sprague-Dawley rats and mice. METHODS AND
resultsIn rats, AT2R activation with intravenous C-21 increased urinary sodium excretion by 10-fold (P<0.0001); this natriuresis was abolished by direct renal interstitial infusion of specific AT2R antagonist PD-123319. C-21 increased fractional excretion of Na(+) (P<0.05) and lithium (P<0.01) without altering renal hemodynamic function. AT2R activation increased renal proximal tubule cell apical membrane AT2R protein (P<0.001) without changing total AT2R expression and internalized/inactivated Na(+)-H(+) exchanger-3 and Na(+)/K(+)ATPase. C-21-induced natriuresis was accompanied by an increase in renal interstitial cGMP (P<0.01); C-21-induced increases in urinary sodium excretion and renal interstitial cGMP were abolished by renal interstitial nitric oxide synthase inhibitor l-N(6)-nitroarginine methyl ester or bradykinin B2 receptor antagonist icatibant. Renal AT2R activation with C-21 prevented Na(+) retention and lowered blood pressure in the angiotensin II infusion model of experimental hypertension.
conclusionsAT2R activation initiates its translocation to the renal proximal tubule cell apical membrane and the internalization of Na(+)-H(+) exchanger-3 and Na(+)/K(+)ATPase, inducing natriuresis in a bradykinin-nitric oxide-cGMP-dependent manner. Intrarenal AT2R activation prevents Na(+) retention and lowers blood pressure in angiotensin II-dependent hypertension. AT2R activation holds promise as a renal proximal tubule natriuretic/diuretic target for the treatment of fluid-retaining states and hypertension.
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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.