ArticleHypertension research : official journal of the Japanese Society of Hypertension2010
A small difference in the molecular structure of angiotensin II receptor blockers induces AT₁ receptor-dependent and -independent beneficial effects.
Article in Hypertension research : official journal of the Japanese Society of Hypertension, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 53 citations in OpenAlex.
- Improvement of Erectile Function After Switching From Valsartan to Olmesartan Within a Fixed-Dose Antihypertensive Combination: A Case Report.Clinical case reports · 2026Article
- The Conventional and Alternative Therapeutic Approaches in Arterial Stiffness Management.Pharmaceutics · 2026Review
- Dataset for discovering new hypertension small molecules using machine learning-aided computational fragment-based design.Data in brief · 2024Article
- The renin-angiotensin-aldosterone system: a new look at an old system.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- Aptamer-assisted two-point immobilized agonist-bound angiotensin II type 1 receptor for a second-site modulator discovery.iScience · 2022Article
- Angiotensin II Receptor Blocker Irbesartan Enhanced SIRT1 longevity Signaling Replaces the Mitochondrial Biogenetic Survival Pathway to Attenuate Hypertension-Induced Heart Apoptosis.Journal of cardiovascular development and disease · 2022Article
- Arterial Hypertension-Oxidative Stress and Inflammation.Antioxidants (Basel, Switzerland) · 2022Review
- Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway.Scientific reports · 2021Article
- Visceral adiposity and high adiponectin levels are associated with the prevalence of pancreatic cystic lesions.International journal of obesity (2005) · 2019Article
- Depressor and Anti-Inflammatory Effects of Angiotensin II Receptor Blockers in Metabolic and/or Hypertensive Patients With Coronary Artery Disease: A Randomized, Prospective Study (DIAMOND Study).Journal of clinical medicine research · 2016Article
- Renin-angiotensin system blockers regulate the metabolism of isolated fat cells in vitro.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2016Article
- Angiotensin II receptor blocker irbesartan attenuates cardiac dysfunction induced by myocardial infarction in the presence of renal failure.Hypertension research : official journal of the Japanese Society of Hypertension · 2016Article
- International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli [corrected].Pharmacological reviews · 2015Review
- Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression.Scientific reports · 2015Article
- Losartan Inhibits Nuclear Factor-κB Activation Induced by Small, Dense LDL Cholesterol Particles in Human Umbilical Vein Endothelial Cells.Current therapeutic research, clinical and experimental · 2014Article
- Telmisartan ameliorates glutamate-induced neurotoxicity: roles of AT(1) receptor blockade and PPARγ activation.Neuropharmacology · 2014Article
- Effects of Ang II receptor blocker irbesartan on adipose tissue function in mice with metabolic disorders.International journal of medical sciences · 2014Article
- Article
- Unique binding behavior of the recently approved angiotensin II receptor blocker azilsartan compared with that of candesartan.Hypertension research : official journal of the Japanese Society of Hypertension · 2013Article
- Reassessment of the unique mode of binding between angiotensin II type 1 receptor and their blockers.PloS one · 2013Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Angiotensin II (Ang II) type 1 (AT₁) receptor blockers (ARBs) induce multiple pharmacological beneficial effects, but not all ARBs have the same effects and the molecular mechanisms underlying their actions are not certain. In this study, irbesartan and losartan were examined because of their different molecular structures (irbesartan has a cyclopentyl group whereas losartan has a chloride group). We analyzed the binding affinity and production of inositol phosphate (IP), monocyte chemoattractant protein-1 (MCP-1) and adiponectin. Compared with losartan, irbesartan showed a significantly higher binding affinity and slower dissociation rate from the AT₁ receptor and a significantly higher degree of inverse agonism and insurmountability toward IP production. These effects of irbesartan were not seen with the AT₁-Y113A mutant receptor. On the basis of the molecular modeling of the ARBs-AT₁ receptor complex and a mutagenesis study, the phenyl group at Tyr(113) in the AT₁ receptor and the cyclopentyl group of irbesartan may form a hydrophobic interaction that is stronger than the losartan-AT₁ receptor interaction. Interestingly, irbesartan inhibited MCP-1 production more strongly than losartan. This effect was mediated by the inhibition of nuclear factor-kappa B activation that was independent of the AT₁ receptor in the human coronary endothelial cells. In addition, irbesartan, but not losartan, induced significant adiponectin production that was mediated by peroxisome proliferator-activated receptor-γ activation in 3T3-L1 adipocytes, and this effect was not mediated by the AT₁ receptor. In conclusion, irbesartan induced greater beneficial effects than losartan due to small differences between their molecular structures, and these differential effects were both dependent on and independent of the AT₁ receptor.
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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.