ArticleThe Journal of clinical investigation1999
Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 559 citations in OpenAlex.
- Comparative effects of angiotensin receptor blockade and ACE inhibition on the fibrinolytic and inflammatory responses to cardiopulmonary bypass.Clinical pharmacology and therapeutics · 2012Trial
- Angiotensin II: a major regulator of subcutaneous adipose tissue blood flow in humans.The Journal of physiology · 2006Trial
- Disparate systemic and renal blocking properties of angiotensin II antagonists during exogenous angiotensin II administration: implications for treatment.Journal of human hypertension · 2004Trial
- A multi-tissue mendelian randomization method based on eQTL data for mapping tissue-specific disease genes.BMC bioinformatics · 2026Article
- Investigating angiotensin II concentration in modulatingFrontiers in parasitology · 2026Article
- Brain AT1 and AT2 receptors and nitric oxide in baroreflex regulation of renal sympathetic activity in unanaesthetised rats.Scientific reports · 2025Article
- The bradykinin-forming cascade in anaphylaxis and ACE-inhibitor induced angioedema/airway obstruction.Frontiers in allergy · 2024Review
- Article
- The ATMolecules (Basel, Switzerland) · 2023Review
- Article
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Counter-regulatory renin-angiotensin system in hypertension: Review and update in the era of COVID-19 pandemic.Biochemical pharmacology · 2023Review
- Cardioprotective Mechanisms against Reperfusion Injury in Acute Myocardial Infarction: Targeting Angiotensin II Receptors.Biomedicines · 2022Review
- CGP42112: the full AT2 receptor agonist and its role in the renin-angiotensin-aldosterone system: no longer misunderstood.Clinical science (London, England : 1979) · 2022Article
- Review
- The Angiotensin ATPharmacological reviews · 2022Review
- Crosstalk between the renin-angiotensin, complement and kallikrein-kinin systems in inflammation.Nature reviews. Immunology · 2022Review
- Angiotensin-(1-7) as a Potential Therapeutic Strategy for Delayed Cerebral Ischemia in Subarachnoid Hemorrhage.Frontiers in immunology · 2022Review
- Class A and C GPCR Dimers in Neurodegenerative Diseases.Current neuropharmacology · 2022Review
- Review
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiotensin II (Ang II) is a potent vasopressor peptide that interacts with 2 major receptor isoforms - AT1 and AT2. Although blood pressure is increased in AT2 knockout mice, the underlying mechanisms remain undefined because of the low levels of expression of AT2 in the vasculature. Here we overexpressed AT2 in vascular smooth muscle (VSM) cells in transgenic (TG) mice. Aortic AT1 was not affected by overexpression of AT2. Chronic infusion of Ang II into AT2-TG mice completely abolished the AT1-mediated pressor effect, which was blocked by inhibitors of bradykinin type 2 receptor (icatibant) and nitric oxide (NO) synthase (L-NAME). Aortic explants from TG mice showed greatly increased cGMP production and diminished Ang II-induced vascular constriction. Removal of endothelium or treatment with icatibant and L-NAME abolished these AT2-mediated effects. AT2 blocked the amiloride-sensitive Na(+)/H(+) exchanger, promoting intracellular acidosis in VSM cells and activating kininogenases. The resulting enhancement of aortic kinin formation in TG mice was not affected by removal of endothelium. Our results suggest that AT2 in aortic VSM cells stimulates the production of bradykinin, which stimulates the NO/cGMP system in a paracrine manner to promote vasodilation. Selective stimulation of AT2 in the presence of AT1 antagonists is predicted to have a beneficial clinical effect in controlling blood pressure.
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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.