Renin–angiotensin system: Basic and clinical aspects—A general perspective
Open accessAbstract
The renin-angiotensin system (RAS) is one of the most complex hormonal regulatory systems, involving several organs that interact to regulate multiple body functions. The study of this system initially focused on investigating its role in the regulation of both cardiovascular function and related pathologies. From this approach, pharmacological strategies were developed for the treatment of cardiovascular diseases. However, new findings in recent decades have suggested that the RAS is much more complex and comprises two subsystems, the classic RAS and an alternative RAS, with antagonistic effects that are usually in equilibrium. The classic system is involved in pathologies where inflammatory, hypertrophic and fibrotic phenomena are common and is related to the development of chronic diseases that affect various body systems. This understanding has been reinforced by the evidence that local renin-angiotensin systems exist in many tissue types and by the role of the RAS in the spread and severity of COVID-19 infection, where it was discovered that viral entry into cells of the respiratory system is accomplished through binding to angiotensin-converting enzyme 2, which is present in the alveolar epithelium and is overexpressed in patients with chronic cardiometabolic diseases. In this narrative review, preclinical and clinical aspects of the RAS are presented and topics for future research are discussed some aspects are raised that should be clarified in the future and that call for further investigation of this system.
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The ACE-Ang II-AT1/2R and ACE2-Ang(1-7)-MasR pathways restrict each other and jointly maintain the relative stability of the internal environment.
“Up till now, two key polypeptides in RAS as well as their enzymes and receptors constitute two core pathways in this system, ACE-Ang II-AT1/2R and ACE2-Ang(1–7)-MasR, which restrict each other and jointly maintain the relative stability of the internal environment [28–30].”
From Transplantation of human umbilical cord-derived mesenchymal stem cells improves age-related ovarian functional decline via regulating the local renin–angiotensin system on inflammation and oxidative stress (2024) · cites this paper as [28]
The “Classic RAS vs alternative RAS” section says the ACE2/Ang1-7/MAS axis counter-regulates the classic ACE/AngII/AT1 axis, and its Figure 1 caption describes the two systems as being in balance (page unavailable). The paper does not place AT2 in the classic axis: its high-blood-pressure section says AT2 activation has effects opposite to AT1 activation. Thus the balancing relationship is supported, but the claimed ACE–Ang II–AT1/2R grouping is not. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAng(1-7) counteracts the overactivated Ang II axis.
“In particular, we should not ignore the counteracting effect of Ang(1–7) on the overactivated Ang II axis [28–30].”
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Genetic Variations Related to Angiotensin II Production and Risk for Basal Cell Carcinoma
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Effects of Dietary Fiber and Acetate on Alcoholic Heart Disease and Intestinal Microbes in Mice
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EFFECT OF TISSUE ANGIOTENSINS ON CARDIOVASCULAR SYSTEM ELEMENTS (LECTURE)
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An Anatomist's View on the Crosstalk Between the Liver and the Lung
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- Authors
- Vargas Vargas, R. A., Varela Millán, J. M., & Fajardo Bonilla, E.
- Venue
- Endocrinología, Diabetes y Nutrición (English ed.)
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 69
- Issue
- 1
- Pages
- 52-62
- ISSN
- 2530-0180 (ISSN-L)
- PMC
- PMC8882059
- OpenAlex
- W4214515006
- Cited by
- 51
- References
- 70
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 22 · 2023: 5 · 2022: 2
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinología Diabetes y Nutrición (English ed ) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- renin-angiotensin system, local renin-angiotensin system, angiotensin-converting enzyme 2, COVID-19 pandemic, cardiovascular disease, hypertension, heart failure, fibrosis, inflammation, cardiometabolic disease, renin-angiotensin system inhibitors, ACE inhibitors, angiotensin receptor blockers
- MeSH terms
- COVID-19, SARS-CoV-2, Cardiovascular Diseases, Humans, Renin-Angiotensin System
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