ArticleThe Journal of clinical investigation2004
Involvement of chymase-mediated angiotensin II generation in blood pressure regulation.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 99 citations in OpenAlex.
- Telmisartan reduces systemic inflammation and alters the renin-angiotensin system in mild COVID-19.Scientific reports · 2025Trial
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- Human Lung Mast Cells as a Possible Reservoir for Coronavirus: A Novel Unrecognized Mechanism for SARS-CoV-2 Immune-Mediated Pathology.International journal of molecular sciences · 2024Article
- Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19.The Journal of clinical investigation · 2023Article
- Review
- Sex differences in the renin-angiotensin-aldosterone system and its roles in hypertension, cardiovascular, and kidney diseases.Frontiers in cardiovascular medicine · 2023Review
- An unusual presentation of anaphylaxis with severe hypertension: a case report.Journal of medical case reports · 2022Article
- Article
- Review
- Persistently Increased Systemic ACE2 Activity Is Associated With an Increased Inflammatory Response in Smokers With COVID-19.Frontiers in physiology · 2021Article
- Innate Immune Cells in Pressure Overload-Induced Cardiac Hypertrophy and Remodeling.Frontiers in cell and developmental biology · 2021Review
- Mast Cell Chymase and Kidney Disease.International journal of molecular sciences · 2020Review
- Covid-19 and the Renin Angiotensin System: Implications for the Older Adults.The journal of nutrition, health & aging · 2020Review
- The renin-angiotensin system: going beyond the classical paradigms.American journal of physiology. Heart and circulatory physiology · 2019Review
- Glutathione prevents chronic oscillating glucose intake-induced β-cell dedifferentiation and failure.Cell death & disease · 2019Article
- Mast Cells in Cardiac Fibrosis: New Insights Suggest Opportunities for Intervention.Frontiers in immunology · 2019Review
- Article
- The pathophysiology of anaphylaxis.The Journal of allergy and clinical immunology · 2017Review
- Intracrine angiotensin II functions originate from noncanonical pathways in the human heart.American journal of physiology. Heart and circulatory physiology · 2016Review
- Mast Cell Inhibition Attenuates Cardiac Remodeling and Diastolic Dysfunction in Middle-aged, Ovariectomized Fischer 344 × Brown Norway Rats.Journal of cardiovascular pharmacology · 2016Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiotensin I-converting enzyme (ACE) inhibitors are thought to lower blood pressure in hypertensive patients, mainly by decreasing angiotensin II (Ang II) formation. Chymase, a human mast cell protease, has recently been proposed to play a role in blood pressure regulation because of its Ang II-forming activity. Here we show that the predominant chymase mRNA species in the mouse aorta are those for types 4 and 5 isoforms, and that both are efficient Ang II-forming enzymes. Evaluation of ACE-dependent and ACE-independent Ang II-forming pathways in mast cell-deficient (Kit(w)/Kit(w-v)) mice and their mast cell-sufficient littermate (MC(+/+)) controls revealed that, in contrast to the latter, Kit(w)/Kit(w-v) mice fail to express chymase mRNAs in the vasculature and have almost no ACE-independent Ang II-forming activity in either isolated blood vessels or homogenates. Moreover, in MC(+/+) but not in Kit(w)/Kit(w-v) mice, a contribution of ACE-independent Ang II generation to blood pressure regulation was evident by a 1.6-fold greater maximal reduction in mean arterial pressure with acute ACE inhibition plus AT(1) receptor blockade than with ACE inhibition alone. Thus, mast cells are the source of the vascular ACE-independent pathway, and the antihypertensive benefit of combining ACE inhibitor therapy with AT(1) receptor antagonist therapy is most likely due to negation of chymase-catalyzed Ang II generation.
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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.