ArticleBritish journal of pharmacology2010
Stimulation of angiotensin AT2 receptors by the non-peptide agonist, Compound 21, evokes vasodepressor effects in conscious spontaneously hypertensive rats.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 138 citations in OpenAlex.
- Stimulation of Angiotensin II Receptor Subtype 2 Reduces Preeclampsia-like Symptoms in a Mouse Model of Preeclampsia.Current issues in molecular biology · 2024Article
- Unlocking the protective potential of the angiotensin type 2 receptor (ATBiochemical pharmacology · 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
- Angiotensin II type 2 receptor-mediated dilation is greater in the cutaneous microvasculature of premenopausal women compared with men.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- Acute In Vivo Administration of Compound 21 Stimulates Akt and ERK1/2 Phosphorylation in Mouse Heart and Adipose Tissue.International journal of molecular sciences · 2023Article
- Restoring Angiotensin Type 2 Receptor Function Reverses PFOS-Induced Vascular Hyper-Reactivity and Hypertension in Pregnancy.International journal of molecular sciences · 2023Article
- The Angiotensin ATPharmacological reviews · 2022Review
- AT2 activation does not influence brain damage in the early phase after experimental traumatic brain injury in male mice.Scientific reports · 2022Article
- Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting.Pharmacological reviews · 2022Review
- The Protective Effects of Compound 21 and Valsartan in Isoproterenol-Induced Myocardial Injury in Rats.Cardiovascular toxicology · 2021Article
- The Brain AT2R-a Potential Target for Therapy in Alzheimer's Disease and Vascular Cognitive Impairment: a Comprehensive Review of Clinical and Experimental Therapeutics.Molecular neurobiology · 2020Review
- Renal functional effects of the highly selective AT2R agonist, β-Pro7 Ang III, in normotensive rats.Clinical science (London, England : 1979) · 2020Article
- Protective effects of losartan on some type 2 diabetes mellitus-induced complications in Wistar and spontaneously hypertensive rats.Metabolic brain disease · 2020Article
- Dose-response, therapeutic time-window and tPA-combinatorial efficacy of compound 21: A randomized, blinded preclinical trial in a rat model of thromboembolic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Reversal of Aortic Enlargement Induced by Increased Biomechanical Forces Requires AT1R Inhibition in Conjunction With AT2R Activation.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Novel Medical Treatments for Hypertension and Related Comorbidities.Current hypertension reports · 2018Review
- Dimerization of ATCurrent hypertension reports · 2018Review
- NADPH Oxidases and Mitochondria in Vascular Senescence.International journal of molecular sciences · 2018Review
- The Effect of a Nonpeptide Angiotensin II Type 2 Receptor Agonist, Compound 21, on Aortic Aneurysm Growth in a Mouse Model of Marfan Syndrome.Journal of cardiovascular pharmacology · 2018Article
- Direct Activation of Angiotensin II Type 2 Receptors Enhances Muscle Microvascular Perfusion, Oxygenation, and Insulin Delivery in Male Rats.Endocrinology · 2018Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeAngiotensin type 2 receptor (AT(2) receptor) stimulation evokes vasodilator effects in vitro and in vivo that oppose the vasoconstrictor effects of angiotensin type 1 receptors (AT(1) receptors). Recently, a novel non-peptide AT(2) receptor agonist, Compound 21, was described, which exhibited high AT(2) receptor selectivity. EXPERIMENTAL APPROACH: Functional cardiovascular effects of the drug candidate Compound 21 were assessed, using mouse isolated aorta and rat mesenteric arteries in vitro and in conscious spontaneously hypertensive rats (SHR). KEY
resultsCompound 21 evoked dose-dependent vasorelaxations in aortic and mesenteric vessels, abolished by the AT(2) receptor antagonist, PD123319. In vivo, Compound 21 administered alone, at doses ranging from 50 to 1000 ng.kg(-1).min(-1) over 4 h did not decrease blood pressure in conscious normotensive Wistar-Kyoto rats or SHR. However, when given in combination with the AT(1) receptor antagonist, candesartan, Compound 21 (300 ng.kg(-1).min(-1)) lowered blood pressure in SHR only. Further analysis in separate groups of conscious SHR revealed that, at a sixfold lower dose, Compound 21 (50 ng.kg(-1).min(-1)) still evoked a significant depressor response in adult SHR ( approximately 30 mmHg) when combined with different doses of candesartan (0.01 or 0.1 mg.kg(-1)). Moreover, the Compound 21-evoked depressor effect was abolished when co-infused (50 microg.kg(-1).min(-1) for 2 h) with the AT(2) receptor antagonist PD123319. CONCLUSION AND IMPLICATIONS: Collectively, our results indicate that acute administration of Compound 21 evoked blood pressure reductions via AT(2) receptor stimulation. Thus Compound 21 can be considered an excellent drug candidate for further study of AT(2) receptor function in cardiovascular disease.
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