ArticleHypertension (Dallas, Tex. : 1979)2014
Angiotensin-converting enzyme 2-independent action of presumed angiotensin-converting enzyme 2 activators: studies in vivo, ex vivo, and in vitro.
Article in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
67 citing papers in PubMed, 114 citations in OpenAlex.
- ACE2-like Catalytic Activity in Anti-SARS-CoV-2 Spike Protein Monoclonal Antibodies.Pathogens (Basel, Switzerland) · 2026Article
- Microglial activation and RAS signaling: a dual-edged sword in neuroinflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Review
- Aminopeptidase A Effect on Angiotensin Peptides and Their Blood Pressure Action.International journal of molecular sciences · 2025Article
- Diminazene Aceturate (DIZE) Ameliorates Hypertension and Induces Anxiolytic- and Antidepressant-like Effects in TGR(mRen2)27.Protein and peptide letters · 2025Article
- Activation of limbal epithelial proliferation is partly controlled by the ACE2-LCN2 pathway.iScience · 2024Article
- Alternative Renin-Angiotensin System.Hypertension (Dallas, Tex. : 1979) · 2024Review
- The Salutary Effects of Diminazene, Lisinopril or Valsartan on Cisplatin - Induced Acute Kidney Injury in Rats: A Comparative Study.Physiological research · 2024Article
- Discovery, validation, and prodrug design of an ACE2 activator for treating bacterial infection-induced lung inflammation.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Diminazene aceturate exacerbates renal fibrosis after unilateral ureteral obstruction in female mice.Kidney research and clinical practice · 2023Article
- Counter-regulatory renin-angiotensin system in hypertension: Review and update in the era of COVID-19 pandemic.Biochemical pharmacology · 2023Review
- Review
- Effects of Taxifolin in Spontaneously Hypertensive Rats with a Focus on Erythrocyte Quality.Life (Basel, Switzerland) · 2022Article
- Is Diminazene an Angiotensin-Converting Enzyme 2 (ACE2) Activator? Experimental Evidence and Implications.The Journal of pharmacology and experimental therapeutics · 2022Article
- Diminazene aceturate attenuates hepatic ischemia/reperfusion injury in mice.Scientific reports · 2022Article
- The COVID-19 pandemic and Alzheimer's disease: mutual risks and mechanisms.Translational neurodegeneration · 2022Review
- Diminazene Aceturate Reduces Angiotensin II Constriction and Interacts with the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2.Biomedicines · 2022Article
- Angiotensin-converting enzyme 2 (ACE2): Two decades of revelations and re-evaluation.Peptides · 2022Review
- Imatinib and methazolamide ameliorate COVID-19-induced metabolic complications via elevating ACE2 enzymatic activity and inhibiting viral entry.Cell metabolism · 2022Article
- An Adverse Outcomes Approach to Study the Effects of SARS-CoV-2 in 3D Organoid Models.Journal of molecular biology · 2022Review
- The interacting physiology of COVID-19 and the renin-angiotensin-aldosterone system: Key agents for treatment.Pharmacology research & perspectives · 2022Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Angiotensin (Ang)-converting enzyme 2 (ACE2) is a key enzyme in the metabolism of Ang II. XNT (1-[(2-dimethylamino)ethylamino]-4-(hydroxymethyl)-7-[(4-methylphenyl) sulfonyl oxy]-9H-xanthene-9-one) and diminazene have been reported to exert various organ-protective effects, which are attributed to the activation of ACE2. To test the effect of these compounds, we studied Ang II degradation in vivo and in vitro as well as their effect on ACE2 activity in vivo and in vitro. In a model of Ang II-induced acute hypertension, blood pressure (BP) recovery was markedly enhanced by XNT (slope with XNT, -3.26±0.2 versus -1.6±0.2 mm Hg/min without XNT; P<0.01). After Ang II infusion, neither plasma nor kidney ACE2 activity was affected by XNT. Plasma Ang II and Ang (1-7) levels also were not significantly affected by XNT. The BP-lowering effect of XNT seen in wild-type animals was also observed in ACE2 knockout mice (slope with XNT, -3.09±0.30 versus -1.28±0.22 mm Hg/min without XNT; P<0.001). These findings show that the BP-lowering effect of XNT in Ang II-induced hypertension cannot be because of the activation of ACE2. In vitro and ex vivo experiments in both mice and rat kidney confirmed a lack of enhancement of ACE2 enzymatic activity by XNT and diminazene. Moreover, Ang II degradation in vitro and ex vivo was unaffected by XNT and diminazene. We conclude that the biological effects of these compounds are ACE2-independent and should not be attributed to the activation of this enzyme.
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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.