Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (872 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin I; angiotensin II; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Renin Angiotensin System; System, Renin-Angiotensin; Renin-Angiotensin-Aldosterone System; Renin Angiotensin Aldosterone System; System, Renin-Angiotensin-Aldosterone.
Where it fits in the MeSH classification
- Broader topics
- Metabolism; Hemodynamics
- See also
- Angiotensin-Converting Enzyme Inhibitors; Kallikrein-Kinin System
Related concepts
- Blood Pressure
- Renin
- Angiotensinogen
- Angiotensin Converting Enzyme
- Angiotensin
- Vascular Smooth Muscle
- Kidney
- Aldosterone
- Adrenal Cortex
- Bradykinin
Research landscape
PubMed indexes 20,868 records tagged with the MeSH heading “Renin-Angiotensin System” (counts retrieved 2026-10-29). 3,590 of them (17.2%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 6,015 records.
Reviews account for 7,890 records (37.8%) and meta-analyses for 277. Randomized controlled trials number 729 (3.5%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 5,984 |
| 2000-2009 | 5,279 |
| 2010-2019 | 6,015 |
| 2020 onward | 3,590 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 7,890 | 37.8% |
| Meta-analyses | 277 | 1.3% |
| Randomized controlled trials | 729 | 3.5% |
Method: PubMed query "Renin-Angiotensin System"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in cardiovascular medicine
Cardiovascular medicine has an unusually large body of randomized trials, so the type of outcome matters: hard clinical events such as death, heart attack and stroke carry more weight than changes in blood pressure, cholesterol or imaging markers that only predict risk. Observational studies can show associations but are confounded by age, lifestyle and other illness. Check whether a result is about prevention or treatment, the baseline risk of participants, and the absolute rather than only the relative size of any benefit.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Renin-Angiotensin-Aldosterone System | 2021 | Review article Design not recorded in structured metadata | 113 | cc by PMID 34745006 · DOI · PMC8567993 |
| Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity | 2022 | Research article Design not recorded in structured metadata | 108 | cc by PMID 35264564 · DOI · PMC8907309 |
| Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD | 2021 | Review article Design not recorded in structured metadata | 105 | cc by PMID 34206708 · DOI · PMC8269397 |
| RAAS antagonists dampen the SARS-CoV-2 infection in ex-vivo cultured human precision-cut lung slices | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 41530760 · DOI · PMC12849188 |
Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Renin-Angiotensin-Aldosterone System [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Sodium-glucose cotransporters inhibitors (SGLT2-i) and GLP-1 receptor agonists (GLP1-RA) are glucose-lowering drugs that are proved to reduce the cardiovascular (CV) risk in type 2 diabetes mellitus (T2DM).
- Closing excerpt
- In conclusion, both SGLT2-i and GLP1-RA seem to have several effects on RAAS, though additional studies are needed to clarify this relationship.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (248 words)
Sodium-glucose cotransporters inhibitors (SGLT2-i) and GLP-1 receptor agonists (GLP1-RA) are glucose-lowering drugs that are proved to reduce the cardiovascular (CV) risk in type 2 diabetes mellitus (T2DM). In this process, the renin-angiotensin-aldosterone system (RAAS) is assumed to play a role. The inhibition of SGLT2 improves hyperglycemia hampering urinary reabsorption of glucose and inducing glycosuria. This "hybrid" diuretic effect, which couples natriuresis with osmotic diuresis, potentially leads to systemic RAAS activation. However, the association between SGLT2-i and systemic RAAS activation is not straightforward. Available data indicate that SGLT2-i cause plasma renin activity (PRA) increase in the early phase of treatment, while PRA and aldosterone levels remain unchanged in chronic treated patients. Furthermore, emerging studies provide evidence that SGLT2-i might have an interfering effect on aldosterone/renin ratio (ARR) in patients with T2DM, due to their diuretic and sympathoinhibition effects. The cardio- and reno-protective effects of GLP-1-RA are at least in part related to the interaction with RAAS. In particular, GLP1-RA counteract the action of angiotensin II (ANG II) inhibiting its synthesis, increasing the inactivation of its circulating form and contrasting its action on target tissue like glomerular endothelial cells and cardiomyocytes. Furthermore, GLP1-RA stimulate natriuresis inhibiting Na+/H+ exchanger NHE-3, which is conversely activated by ANG II. Moreover, GLP1 infusion acutely reduces circulating aldosterone, but this effect does not seem to be chronically maintained in patients treated with GLP1-RA. In conclusion, both SGLT2-i and GLP1-RA seem to have several effects on RAAS, though additional studies are needed to clarify this relationship.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34745006 · DOI · PMC8567993
Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity [2]
Abstract reading summary — source excerpts
- Opening excerpt
- COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases.
- Closing excerpt
- Although our current and previous studies identify anti-GPCR antibodies as natural components of human biology, their production is deregulated in COVID-19 and their level and pattern alterations might predict COVID-19 disease severity.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (160 words)
COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. In order to understand the role of these immune globulins in the pathogenesis of the disease, it is important to explore the autoantibody spectra. Here we show, by a cross-sectional study of 246 individuals, that autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules associate with the clinical severity of COVID-19. Patients with moderate and severe disease are characterized by higher autoantibody levels than healthy controls and those with mild COVID-19 disease. Among the anti-GPCR autoantibodies, machine learning classification identifies the chemokine receptor CXCR3 and the RAS-related molecule AGTR1 as targets for antibodies with the strongest association to disease severity. Besides antibody levels, autoantibody network signatures are also changing in patients with intermediate or high disease severity. Although our current and previous studies identify anti-GPCR antibodies as natural components of human biology, their production is deregulated in COVID-19 and their level and pattern alterations might predict COVID-19 disease severity.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35264564 · DOI · PMC8907309
Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury.
- Closing excerpt
- In this review, we also summarize the data on treatment approaches involving cytokine targeting in CVD, which can contribute to a better understanding of atherogenesis and even its prevention.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (238 words)
Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury. There are no effective treatment options, as well as preventive measures for atherosclerosis. However, this disease has various severe complications, the most severe of which is cardiovascular disease (CVD). It is important to note, that CVD is among the leading causes of death worldwide. The renin-angiotensin-aldosterone system (RAAS) is an important part of inflammatory response regulation. This system contributes to the recruitment of inflammatory cells to the injured site and stimulates the production of various cytokines, such as IL-6, TNF-a, and COX-2. There is also an association between RAAS and oxidative stress, which is also an important player in atherogenesis. Angiotensin-II induces plaque formation at early stages, and this is one of the most crucial impacts on atherogenesis from the RAAS. Importantly, while stimulating the production of ROS, Angiotensin-II at the same time decreases the generation of NO. The endothelium is known as a major contributor to vascular function. Oxidative stress is the main trigger of endothelial dysfunction, and, once again, links RAAS to the pathogenesis of atherosclerosis. All these implications of RAAS in atherogenesis lead to an explicable conclusion that elements of RAAS can be promising targets for atherosclerosis treatment. In this review, we also summarize the data on treatment approaches involving cytokine targeting in CVD, which can contribute to a better understanding of atherogenesis and even its prevention.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34206708 · DOI · PMC8269397
RAAS antagonists dampen the SARS-CoV-2 infection in ex-vivo cultured human precision-cut lung slices [4]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundWhile the renin-angiotensin-aldosterone system (RAAS) is critically involved in pathomechanisms related to SARS-CoV-2 infection, the role of ongoing therapy with angiotensin-converting enzyme 1 inhibitors (ACEi) or Angiotensin-II type 1 receptor (AT1R) blockers (ARB) is much less clear.
- Closing excerpt
- In opposite, in an ex-vivo model of human PCLS, such treatment was found to dampen SARS-CoV-2 infection and consecutive inflammation.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (226 words)
BackgroundWhile the renin-angiotensin-aldosterone system (RAAS) is critically involved in pathomechanisms related to SARS-CoV-2 infection, the role of ongoing therapy with angiotensin-converting enzyme 1 inhibitors (ACEi) or Angiotensin-II type 1 receptor (AT1R) blockers (ARB) is much less clear. We evaluated the effects of the ACEi enalapril (ENA) and the ARB losartan (LOS) on SARS-CoV-2 infection in human ex vivo-cultured, precision-cut lung slices (PCLS) obtained from normal human lung tissue.MethodsPCLS were pre-treated for 5d with vehicle, LOS or ENA (300 µM), followed by mock infection or infection with SARS-CoV-2 and incubation with vehicle, LOS or ENA for 1d or 2d. Thereafter, PCLS were harvested for analysis of viral replication, inflammatory responses, endoplasmic reticulum (ER) stress and apoptosis pathways.ResultsBoth LOS and ENA significantly reduced viral replication in PCLS, with ENA being more potent. LOS was more efficient than ENA in reducing the expression of IL1B, CCL2, CXCL2 and TNFA, but not of IL6, whereas ENA preferentially caused a reduction of IL6 and CCL2 in SARS-CoV-2-infected PCLS. Further, ENA, but not LOS, significantly decreased the expression of viral entry factors, ACE2 and transmembrane serine protease 2 (TMPRSS2), in infected PCLS. Importantly, LOS or ENA did not exert cytotoxic effects.ConclusionsRAAS-antagonizing drugs do not seem to exert detrimental effects during SARS-CoV-2 infection. In opposite, in an ex-vivo model of human PCLS, such treatment was found to dampen SARS-CoV-2 infection and consecutive inflammation.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41530760 · DOI · PMC12849188
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Prevention of atrial fibrillation by Renin-Angiotensin system inhibition a meta-analysis [5]
- Research article Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials [6]
- Research article Targeting the renin-angiotensin-aldosterone system in fibrosis [7]
- Research article Clinical Management of Hyperkalemia [8]
- Research article Crosstalk between the renin-angiotensin, complement and kallikrein-kinin systems in inflammation [9]
- Research article Meta-analysis: inhibition of renin-angiotensin system prevents new-onset atrial fibrillation [10]
References
- Puglisi S, Rossini A, Poli R, Dughera F, Pia A, Terzolo M, et al.. Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Renin-Angiotensin-Aldosterone System. . 2021. PMID 34745006 · DOI · PMC8567993
- Cabral-Marques O, Halpert G, Schimke LF, Ostrinski Y, Vojdani A, Baiocchi GC, et al.. Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity. . 2022. PMID 35264564 · DOI · PMC8907309
- Poznyak AV, Bharadwaj D, Prasad G, Grechko AV, Sazonova MA, Orekhov AN. Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD. . 2021. PMID 34206708 · DOI · PMC8269397
- Mahavadi P, Korfei M, Müller-Ruttloff C, Ruppert C, Krauss E, Dorfmüller P, et al.. RAAS antagonists dampen the SARS-CoV-2 infection in ex-vivo cultured human precision-cut lung slices. . 2026. PMID 41530760 · DOI · PMC12849188
- Schneider MP, Hua TA, Böhm M, Wachtell K, Kjeldsen SE, Schmieder RE. Prevention of atrial fibrillation by Renin-Angiotensin system inhibition a meta-analysis. J Am Coll Cardiol. 2010. PMID 20488299 · DOI
- Makani H, Bangalore S, Desouza KA, Shah A, Messerli FH. Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials. BMJ. 2013. PMID 23358488 · DOI · PMC3556933
- AlQudah M, AlQudah M, Hale TM, Czubryt MP. Targeting the renin-angiotensin-aldosterone system in fibrosis. Matrix Biol. 2020. PMID 32422329 · DOI · PMC7434656
- Palmer BF, Carrero JJ, Clegg DJ, Colbert GB, Emmett M, Fishbane S, et al.. Clinical Management of Hyperkalemia. Mayo Clin Proc. 2021. PMID 33160639 · DOI
- Bekassy Z, Lopatko Fagerström I, Bader M, Karpman D. Crosstalk between the renin-angiotensin, complement and kallikrein-kinin systems in inflammation. Nat Rev Immunol. 2022. PMID 34759348 · DOI · PMC8579187
- Anand K, Mooss AN, Hee TT, Mohiuddin SM. Meta-analysis: inhibition of renin-angiotensin system prevents new-onset atrial fibrillation. Am Heart J. 2006. PMID 16875900 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.