ArticleCardiovascular diabetology2014
Azilsartan, an angiotensin II type 1 receptor blocker, restores endothelial function by reducing vascular inflammation and by increasing the phosphorylation ratio Ser(1177)/Thr(497) of endothelial nitric oxide synthase in diabetic mice.
Article in Cardiovascular diabetology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 61 citations in OpenAlex.
- Azilsartan as "Add-On" Treatment with Methotrexate Improves the Disease Activity of Rheumatoid Arthritis.BioMed research international · 2018Trial
- Des-Aspartate Angiotensin-1: A Dual-Targeted Therapeutic for Perivascular Inflammation and Vascular Dysfunction in Obesity.Journal of cardiovascular translational research · 2025Review
- Implication of endoplasmic reticulum stress and mitochondrial perturbations in remote liver injury after renal ischemia/reperfusion in rats: potential protective role of azilsartan.Redox report : communications in free radical research · 2024Article
- Unveiling the Role of Endothelial Dysfunction: A Possible Key to Enhancing Catheter Ablation Success in Atrial Fibrillation.International journal of molecular sciences · 2024Review
- Common mechanisms underlying diabetic vascular complications: focus on the interaction of metabolic disorders, immuno-inflammation, and endothelial dysfunction.Cell communication and signaling : CCS · 2023Review
- A Selective Mineralocorticoid Receptor Blocker, Esaxerenone, Attenuates Vascular Dysfunction in Diabetic C57BL/6 Mice.Journal of atherosclerosis and thrombosis · 2023Article
- Article
- Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling.Frontiers in pharmacology · 2021Article
- Vildagliptin, a dipeptidyl peptidase-4 inhibitor, attenuated endothelial dysfunction through miRNAs in diabetic rats.Archives of medical science : AMS · 2021Article
- The Role of Fibroblast Growth Factor 21 in Diabetic Cardiovascular Complications and Related Epigenetic Mechanisms.Frontiers in endocrinology · 2021Review
- Insights into the actions of angiotensin-1 receptor (AT1R) inverse agonists: Perspectives and implications in COVID-19 treatment.EXCLI journal · 2021Review
- Effect of Switching to Azilsartan From Fixed-Dose Combination of an Angiotensin II Receptor Blocker and Calcium Channel Blocker or a Thiazide in Patients With Hypertension.Journal of clinical medicine research · 2019Article
- Article
- Immunopharmacology of Post-Myocardial Infarction and Heart Failure Medications.Journal of clinical medicine · 2018Review
- Exendin‑4 reverses endothelial dysfunction in mice fed a high‑cholesterol diet by a GTP cyclohydrolase‑1/tetrahydrobiopterin pathway.Molecular medicine reports · 2018Article
- A Possible Mechanism: Vildagliptin Prevents Aortic Dysfunction through Paraoxonase and Angiopoietin-Like 3.BioMed research international · 2018Article
- Effect of Azilsartan on Day-to-Day Variability in Home Blood Pressure: A Prospective Multicenter Clinical Trial.Journal of clinical medicine research · 2017Article
- AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits.Korean circulation journal · 2017Article
- Azilsartan medoxomil in the management of hypertension: an evidence-based review of its place in therapy.Core evidence · 2016Review
- Glycemic Control with Ipragliflozin, a Novel Selective SGLT2 Inhibitor, Ameliorated Endothelial Dysfunction in Streptozotocin-Induced Diabetic Mouse.Frontiers in cardiovascular medicine · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAzilsartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), has a higher affinity for and slower dissociation from AT1 receptors and shows stronger inverse agonism compared to other ARBs. Possible benefits of azilsartan in diabetic vascular dysfunction have not been established.
methodsWe measured vascular reactivity of aortic rings in male KKAy diabetic mice treated with vehicle, 0.005% azilsartan, or 0.005% candesartan cilexetil for 3 weeks. Expression of markers of inflammation and oxidative stress was measured using semiquantitative RT-PCR in the vascular wall, perivascular fat, and skeletal muscle. Phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 and Thr495 was measured using Western blotting, and the ratio of phosphorylation at Ser1177 to phosphorylation at Thr495 was used as a putative indicator of vascular eNOS activity.
results(1) Vascular endothelium-dependent relaxation with acetylcholine in KKAy mice was improved by azilsartan treatment compared to candesartan cilexetil; (2) the ratio of Ser1177/Thr495 phosphorylation of eNOS was impaired in KKAy and was effectively restored by azilsartan; (3) anomalies in the expression levels of monocyte chemotactic protein 1 (MCP1), F4/80, NAD(P)H oxidase (Nox) 2, and Nox4 of the aortic wall and in the expression of TNFα in the perivascular fat were strongly attenuated by azilsartan compared to candesartan cilexetil.
conclusionsThese results provide evidence that azilsartan prevents endothelial dysfunction in diabetic mice, more potently than does candesartan cilexetil. Azilsartan's higher affinity for and slower dissociation from AT1 receptors may underlie its efficacy in diabetic vascular dysfunction via a dual effect on uncoupled eNOS and on Nox.
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