Role of the renin-angiotensin-aldosterone system in sepsis and its therapeutic targets.

An imbalance in the host's response to infection causes sepsis, a potentially fatal condition. Sepsis may advance to septic shock, organ dysfunction (including the brain, liver, lung, kidney, and heart), skeletal muscle atrophy, and an array of severe complications. The renin-angiotensin-aldosterone system (RAAS) undergoes significant alterations during sepsis, and the expression of its principal bioactive components is closely associated with the prognosis of patients with sepsis. Targeting RAAS may offer an effective approach to managing sepsis and its complications. Consequently, this review primarily summarizes the impact of sepsis on the activity and expression of key RAAS components in the circulation and tissues. We also discuss the effects and mechanisms of selectively modulating the RAAS in the context of sepsis and its associated complications. Furthermore, we introduce innovative perspectives on the precise regulation of the RAAS with the aim of optimizing treatment strategies tailored to different stages of sepsis and diverse complications.

• Publication year

  2025

• Venue

  International Immunopharmacology

• Publication date

  2025-07-10

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.intimp.2025.115192PMID 40644863
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Plasma renin as a novel prognostic biomarker of sepsis-associated acute respiratory distress syndrome

  2024cited by this paper
• Higher Circulating  ACE2 and DPP3 but Reduced ACE and Angiotensinogen in Hyperreninemic Sepsis Patients.

  2024cited by this paper
• Dysfunction of the Renin-Angiotensin-Aldosterone System in Human Septic Shock.

  2024cited by this paper
• Stronger association of intact angiotensinogen with mortality than lactate or renin in critical illness: post-hoc analysis from the VICTAS trial

  2024cited by this paper
• Angiotensin 1–7 in an experimental septic shock model

  2023cited by this paper
• Angiotensin-(1–7) ameliorates sepsis-induced cardiomyopathy by alleviating inflammatory response and mitochondrial damage through the NF-κB and MAPK pathways

  2023cited by this paper
• Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials.

  2023cited by this paper
• IMPACT OF THE ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS ON THE COURSE OF THE SEPTIC SHOCK DEVELOPED DURING COVID-19 AND OTHER SEVERE RESPIRATORY INFECTIONS IN PRESENCE OF HYPERFERRITINEMIA.

  2023cited by this paper
• Association of Active Renin Content With Mortality in Critically Ill Patients: A Post hoc Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) Trial*

  2023cited by this paper
• Angiotensin-(1-7) improves tail skin heat loss and increases the survival of rats with polymicrobial sepsis.

  2023cited by this paper
• Stimulation of angiotensin II type 2 receptor attenuates organ injury in rats with polymicrobial sepsis

  2023cited by this paper
• Utilization of Synthetic Human Angiotensin II for Catecholamine-Resistant Vasodilatory Shock in Critically Ill Children: A Single-Center Retrospective Case Series

  2023cited by this paper
• Recombinant human angiotensin-converting enzyme 2 plays a protective role in mice with sepsis-induced cardiac dysfunction through multiple signaling pathways dependent on converting angiotensin II to angiotensin 1–7

  2023cited by this paper
• Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.

  2023cited by this paper
• Micro-lightguide spectrophotometry assessment of hepatic and intestinal microcirculation in endotoxemic rats during intravenous treatment with angiotensin II.

  2023cited by this paper
• Investigating the renoprotective effect of C21 in male mice with sepsis via modulation of p-AKT/PI3K expression

  2023cited by this paper
• Increasing angiotensin-converting enzyme concentrations and absent angiotensin-converting enzyme activity are associated with adverse kidney outcomes in pediatric septic shock

  2023cited by this paper
• Trajectory of PaO2/FiO2 Ratio in Shock After Angiotensin II

  2023cited by this paper
• Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial

  2023cited by this paper
• Potential therapeutic implications of calcitriol administration and weight reduction on CD4 T cell dysregulation and renin angiotensin system-associated acute lung injury in septic obese mice.

  2023cited by this paper
• Serum renin and prorenin concentrations predict severe persistent acute kidney injury and mortality in pediatric septic shock

  2023cited by this paper
• Assessing the outcomes of prescribing angiotensin converting enzyme inhibitors and angiotensin receptor blockers for COVID-19 patients

  2023cited by this paper
• CORRELATIVE ASSOCIATION OF OXYGENATION AND SEPSIS PANELS WITH THE USE OF ACE2 INHIBITORS AND WITHOUT IT IN THE CONDITIONS OF SEPTIC SHOCK IN COVID-19-INFECTED AND NON-INFECTED PATIENTS (COHORT STUDY).

  2023cited by this paper
• Angiotensin II enhances bacterial clearance via myeloid signaling in a murine sepsis model

  2022cited by this paper
• Olmesartan Ameliorates Organ Injury and Mortality in Rats With Peritonitis-Induced Sepsis.

  2022cited by this paper
• Renin as a Marker of Tissue Perfusion, Septic Shock and Mortality in Septic Patients: A Prospective Observational Study

  2022cited by this paper
• How sepsis parallels and differs from COVID-19

  2022cited by this paper
• RAS inhibition and sepsis-associated acute kidney injury.

  2022cited by this paper
• Angiotensin II infusion in COVID‐19: An international, multicenter, registry‐based study

  2022cited by this paper
• Angiotensin II and Angiotensin II receptor 2 levels can predict shock and mortality in septic patients.

  2022cited by this paper
• FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2

  2022cited by this paper
• Construction and Validation of a Risk Prediction Model for Acute Kidney Injury in Patients Suffering from Septic Shock

  2022cited by this paper
• Sacubitril/valsartan alleviates sepsis‐induced acute lung injury via inhibiting GSDMD‐dependent macrophage pyroptosis in mice

  2022cited by this paper
• Hydrocortisone may act through the angiotensin II receptor-2 level in patients with catecholamine-resistant septic shock.

  2022cited by this paper
• Diminazene aceturate mitigates cardiomyopathy by interfering with renin-angiotensin system in a septic rat model

  2022cited by this paper
• The Pretreatment of Xiaoqinglong Decoction Alleviates Inflammation and Oxidative Damage and Up-Regulates Angiotensin-Converting Enzyme 2 in Lipopolysaccharide-Induced Septic Acute Lung Injury Rats

  2022cited by this paper
• Losartan attenuates sepsis-induced cardiomyopathy by regulating macrophage polarization via TLR4-mediated NF-κB and MAPK signaling.

  2022cited by this paper
• Angiotensin II - A Brief Review and Role in Severe SARS-COV-2 Sepsis

  2022cited by this paper
• Renin-Angiotensin System Pathway Therapeutics Associated With Improved Outcomes in Males Hospitalized With COVID-19*

  2022cited by this paper
• A genome-wide association study of survival in patients with sepsis

  2022cited by this paper
• The prognostic importance of the angiotensin II/angiotensin-(1–7) ratio in patients with SARS-CoV-2 infection

  2022cited by this paper
• Unraveling the Differentially Articulated Axes of the Century-Old Renin–Angiotensin–Aldosterone System: Potential Therapeutic Implications

  2022cited by this paper
• ACE2-like enzyme B38-CAP suppresses abdominal sepsis and severe acute lung injury

  2022cited by this paper
• Renin-Angiotensin System Inhibitors and Major Cardiovascular Events after Sepsis.

  2022cited by this paper
• Repressed Ang 1–7 in COVID-19 Is Inversely Associated with Inflammation and Coagulation

  2022cited by this paper
• Sepsis-Induced Brain Dysfunction: Pathogenesis, Diagnosis, and Treatment

  2022cited by this paper
• Myocardial effects of angiotensin II compared to norepinephrine in an animal model of septic shock

  2022cited by this paper
• The Impact of Coronavirus Disease 2019 (COVID-19) on Healthcare-Associated Infections

  2021cited by this paper
• Increased Angiotensin-Converting Enzyme 2 and Loss of Alveolar Type II Cells in COVID-19–related Acute Respiratory Distress Syndrome

  2021cited by this paper
• Dysregulation of the renin-angiotensin system in septic shock: mechanistic insights and application of angiotensin II in clinical management.

  2021cited by this paper
• COVID‐19 and the impact of arterial hypertension—An analysis of the international HOPE COVID‐19 Registry (Italy‐Spain‐Germany)

  2021cited by this paper
• Crosstalk between the renin–angiotensin, complement and kallikrein–kinin systems in inflammation

  2021cited by this paper
• Trajectory of Cognitive Decline After Sepsis

  2021cited by this paper
• The Level and Significance of Circulating Angiotensin-III in Patients with Coronary Atherosclerosis

  2021cited by this paper
• Prior Exposure to Angiotensin II Receptor Blockers in Patients With Septic Shock to Individualize Mean Arterial Pressure Target? A Post Hoc Analysis of the Sepsis and Mean Arterial Pressure (SEPSISPAM) Trial*

  2021cited by this paper
• Pathophysiology of sepsis-induced cardiomyopathy

  2021cited by this paper
• Coronavirus Disease 2019 as Cause of Viral Sepsis: A Systematic Review and Meta-Analysis*

  2021cited by this paper
• Loss of Hepatic Angiotensinogen Attenuates Sepsis-Induced Myocardial Dysfunction

  2021cited by this paper
• Therapeutic approaches targeting renin-angiotensin system in sepsis and its complications.

  2021cited by this paper
• Alamandine, a derivative of angiotensin-(1-7), alleviates sepsis-associated renal inflammation and apoptosis by inhibiting the PI3K/Ak and MAPK pathways.

  2021cited by this paper
• The ACE2-Ang-(1‑7)-Mas Axis Modulates M1/M2 Macrophage Polarization to Relieve CLP-Induced Inflammation via TLR4-Mediated NF-кb and MAPK Pathways

  2021cited by this paper
• Angiotensin (1-7) Attenuates Sepsis-Induced Acute Kidney Injury by Regulating the NF-κB Pathway

  2021cited by this paper
• Intravenous calcitriol administration regulates the renin-angiotensin system and attenuates acute lung injury in obese mice complicated with polymicrobial sepsis.

  2021cited by this paper
• Angiotensin-(1-7) protects against sepsis-associated left ventricular dysfunction induced by lipopolysaccharide.

  2021cited by this paper
• Cerebral dysfunctions caused by sepsis during ageing

  2021cited by this paper
• Signaling pathways and intervention therapies in sepsis

  2021cited by this paper
• Central Administration of Angiotensin-(1-7) Improves Vasopressin Impairment and Hypotensive Response in Experimental Endotoxemia

  2021cited by this paper
• Renin-angiotensin system and inflammation update.

  2021cited by this paper
• Effects of Renin‐Angiotensin–Aldosterone System Inhibitors on Long‐Term Major Adverse Cardiovascular Events in Sepsis Survivors

  2021cited by this paper
• Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Use Associated with Reduced Mortality and Other Disease Outcomes in US Veterans with COVID-19

  2021cited by this paper
• Cytokine Drizzle—The Rationale for Abandoning “Cytokine Storm”

  2021cited by this paper
• Angiotensin-(1–7) treatment blocks lipopolysaccharide-induced organ damage, platelet dysfunction, and IL-6 and nitric oxide production in rats

  2021cited by this paper
• Angiotensin aldosterone inhibitors improve survival and ameliorate kidney injury induced by sepsis through suppression of inflammation and apoptosis

  2021cited by this paper
• Elevated angiotensin II induces platelet apoptosis through promoting oxidative stress in an AT1R‐dependent manner during sepsis

  2021cited by this paper
• Angiotensin II receptor type 1 blockade improves hyporesponsiveness to vasopressors in septic shock.

  2021cited by this paper
• The cardioprotective effects of perindopril in a model of polymicrobial sepsis: The role of radical oxygen species and the inflammation pathway

  2020cited by this paper
• SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

  2020cited by this paper
• Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Covid-19

  2020cited by this paper
• The Protective Effects of Perindopril Against Acute Kidney Damage Caused by Septic Shock

  2020cited by this paper
• Renin–Angiotensin–Aldosterone System Blockers and the Risk of Covid-19

  2020cited by this paper
• Contemporary Review in Critical Care Medicine:Mitochondria and Critical Illness.

  2020cited by this paper
• Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial.

  2020cited by this paper
• Hypertension, medications, and risk of severe COVID‐19: A Massachusetts community‐based observational study

  2020cited by this paper
• Possible contribution of the neprilysin/ACE pathway to sepsis in mice.

  2020cited by this paper
• Nox2+ Myeloid cells drive vascular inflammation and endothelial dysfunction in heart failure after myocardial infarction via angiotensin II receptor type 1.

  2020cited by this paper
• Immunity, endothelial injury and complement-induced coagulopathy in COVID-19

  2020cited by this paper
• Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area.

  2020cited by this paper
• Impaired angiotensin II type 1 receptor signaling contributes to sepsis induced acute kidney injury.

  2020cited by this paper
• Effects Of ARBs And ACEIs On Virus Infection, Inflammatory Status And Clinical Outcomes In COVID-19 Patients With Hypertension: A Single Center Retrospective Study.

  2020cited by this paper
• Hemodynamic Impact of Cardiovascular Antihypertensive Medications in Patients With Sepsis-Related Acute Circulatory Failure.

  2020cited by this paper
• Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China.

  2020cited by this paper
• Gut-liver crosstalk in sepsis-induced liver injury

  2020cited by this paper
• Central angiotensin-(1-7) attenuates systemic inflammation via activation of sympathetic signaling in endotoxemic rats.

  2020cited by this paper
• Angiotensin‐converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID‐19 infection in a multi‐site UK acute hospital trust

  2020cited by this paper
• Ramipril pretreatment worsened renal injury and survival despite a reduction in renal inflammation in experimentally induced sepsis in mice

  2020cited by this paper
• Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens

  2020cited by this paper
• Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial

  2020cited by this paper
• Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses

  2020cited by this paper
• Preadmission Antihypertensive Drug Use and Sepsis Outcome: Impact of Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs).

  2020cited by this paper
• Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension

  2020cited by this paper

• Physiopathology of the Brain Renin-Angiotensin System

  2025cites this paper
• Novel Aspects of the Renin-Angiotensin-Aldosterone System in Septic Shock

  2025cites this paper