ArticleHypertension research : official journal of the Japanese Society of Hypertension2012
AT2 receptor non-peptide agonist C21 promotes natriuresis in obese Zucker rats.
Article in Hypertension research : official journal of the Japanese Society of Hypertension, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Guideline
- Protein phosphatase 2A subunit B55 alpha is required for angiotensin type 2 receptor elicited natriuresis.American journal of physiology. Renal physiology · 2026Article
- Novel Antihypertensive Medications to Target the Renin-Angiotensin System: Mechanisms and Research.Reviews in cardiovascular medicine · 2025Review
- Macrophage angiotensin ATAmerican journal of physiology. Renal physiology · 2023Article
- The Angiotensin ATPharmacological 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 Type-2 Receptors: Transducers of Natriuresis in the Renal Proximal Tubule.International journal of molecular sciences · 2022Review
- Angiotensin II Type 2 Receptor: A Target for Protection Against Hypertension, Metabolic Dysfunction, and Organ Remodeling.Hypertension (Dallas, Tex. : 1979) · 2021Review
- Combining Neprilysin Inhibitor With ATFrontiers in pharmacology · 2021Article
- Synergism between Angiotensin receptors ligands: Role of Angiotensin-(1-7) in modulating ATPharmacology research & perspectives · 2020Article
- Emerging Role of Angiotensin AT2 Receptor in Anti-Inflammation: An Update.Current pharmaceutical design · 2020Review
- Dimerization of ATCurrent hypertension reports · 2018Review
- Role of ATHypertension (Dallas, Tex. : 1979) · 2018Article
- AT2R (Angiotensin II Type 2 Receptor)-Mediated Regulation of NCC (Na-Cl Cotransporter) and Renal K Excretion Depends on the K Channel, Kir4.1.Hypertension (Dallas, Tex. : 1979) · 2018Article
- Angiotensin II Type 2 Receptor and Receptor Mas Are Colocalized and Functionally Interdependent in Obese Zucker Rat Kidney.Hypertension (Dallas, Tex. : 1979) · 2017Article
- Update on angiotensin AT2 receptors.Current opinion in nephrology and hypertension · 2017Review
- Angiotensin type 2 receptor null mice express reduced levels of renal angiotensin II type 2 receptor/angiotensin (1-7)/Mas receptor and exhibit greater high-fat diet-induced kidney injury.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2016Article
- Enhanced Natriuresis and Diuresis in Wistar Rats Caused by the Costimulation of Renal Dopamine D3 and Angiotensin II Type 2 Receptors.American journal of hypertension · 2015Article
- Angiotensin AT2 receptor agonist prevents salt-sensitive hypertension in obese Zucker rats.American journal of physiology. Renal physiology · 2015Article
- Angiotensin type 2 receptors: blood pressure regulation and end organ damage.Current opinion in pharmacology · 2015Review
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2 authors at 1 institution in 1 country.
Funding
Abstract
Previously, we demonstrated that angiotensin II type 2 (AT(2)) receptors have a role in natriuresis in obese Zucker rats (OZR). In the present study, we investigated the role of a novel, non-peptide agonist, C21, in natriuresis via AT(2) receptor activation in OZR. Infusion of C21 (1 and 5 μg kg(-1) min(-1)) into rats under anesthesia caused a dose-dependent increase in urine flow (UF) and urinary Na volume (U(Na)V). These effects of C21 were blocked by pre-infusion of the AT(2) receptor antagonist, PD123319, (50 μg kg(-1) min(-1)), suggesting involvement of the AT(2) receptor. Infusion of C21 (5 μg kg(-1) min(-1)) significantly increased the fractional excretion of sodium without changing the glomerular filtration rate or blood pressure, suggesting a tubular effect. Similarly, C21 infusion increased the fractional excretion of lithium, suggesting a proximal tubular effect. Furthermore, we tested the effect of C21 on natriuresis after blocking two main, distal-nephron Na transporters, the epithelial Na channels (ENaC), with amiloride (AM, 3 mg kg(-1) body wt), and the NaCl cotransporters (NCC), with bendroflumethiazide (BFTZ, 7 mg kg(-1) body wt). Infusion of AM + BFTZ caused significant increases in both diuresis and natriuresis, which were further increased by infusion of C21 (5 μg kg(-1) min(-1)). Natriuresis in response to C21 was associated with increases in urinary NO and cGMP levels. The data indicate that the AT(2) receptor agonist, C21, promotes natriuresis via AT(2) receptor activation and that this effect is potentially based in the proximal tubules and linked to the nitric oxide/cyclic guanosine monophosphate pathway. The natriuretic response to C21 may have therapeutic significance by improving kidney function in obesity.
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