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Critical Care (London, England) Mar 2018This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at... (Review)
Review
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .
Topics: Angiotensin II; Angiotensins; Critical Care; Humans; Hypotension; Shock, Septic; Vasoconstrictor Agents
PubMed: 29558991
DOI: 10.1186/s13054-018-1995-z -
Pharmacological Reviews Oct 2022Discovered more than 30 years ago, the angiotensin AT receptor (ATR) has evolved from a binding site with unknown function to a firmly established major effector within... (Review)
Review
Discovered more than 30 years ago, the angiotensin AT receptor (ATR) has evolved from a binding site with unknown function to a firmly established major effector within the protective arm of the renin-angiotensin system (RAS) and a target for new drugs in development. The ATR represents an endogenous protective mechanism that can be manipulated in the majority of preclinical models to alleviate lung, renal, cardiovascular, metabolic, cutaneous, and neural diseases as well as cancer. This article is a comprehensive review summarizing our current knowledge of the ATR, from its discovery to its position within the RAS and its overall functions. This is followed by an in-depth look at the characteristics of the ATR, including its structure, intracellular signaling, homo- and heterodimerization, and expression. ATR-selective ligands, from endogenous peptides to synthetic peptides and nonpeptide molecules that are used as research tools, are discussed. Finally, we summarize the known physiological roles of the ATR and its abundant protective effects in multiple experimental disease models and expound on ATR ligands that are undergoing development for clinical use. The present review highlights the controversial aspects and gaps in our knowledge of this receptor and illuminates future perspectives for ATR research. SIGNIFICANCE STATEMENT: The angiotensin AT receptor (ATR) is now regarded as a fully functional and important component of the renin-angiotensin system, with the potential of exerting protective actions in a variety of diseases. This review provides an in-depth view of the ATR, which has progressed from being an enigma to becoming a therapeutic target.
Topics: Angiotensins; Binding Sites; Humans; Ligands; Peptides; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System
PubMed: 36180112
DOI: 10.1124/pharmrev.120.000281 -
Clinical and Experimental Hypertension... 2018Renin angiotensin system (RAS) is an endogenous hormone system involved in the control of blood pressure and fluid volume. Dysregulation of RAS has a pathological role... (Review)
Review
Renin angiotensin system (RAS) is an endogenous hormone system involved in the control of blood pressure and fluid volume. Dysregulation of RAS has a pathological role in causing cardiovascular diseases through hypertension. Among several key components of RAS, angiotensin peptides, varying in amino acid length and biological function, have important roles in preventing or promoting hypertension, cardiovascular diseases, stroke, vascular remodeling etc. These peptides are generated by the metabolism of inactive angiotensinogen or its derived peptides by hydrolyzing action of certain enzymes. Angiotensin II, angiotensin (1-12), angiotensin A and angiotensin III bind primarily to angiotensin II type 1 receptor and cause vasoconstriction, accumulation of inflammatory markers to sub-endothelial region of blood vessels and activate smooth muscle cell proliferation. Moreover, when bound to angiotensin II type 2 receptor, angiotensin II works as cardio-protective peptide and halt pathological cell signals. Other peptides like angiotensin (1-9), angiotensin (1-7), alamandine and angiotensin IV also help in protecting from cardiovascular diseases by binding to their respective receptors.
Topics: Angiotensin I; Angiotensin II; Angiotensin III; Angiotensinogen; Angiotensins; Animals; Blood Pressure; Humans; Hypertension; Oligopeptides; Peptide Fragments; Protective Factors; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System; Signal Transduction; Vasoconstriction
PubMed: 29190205
DOI: 10.1080/10641963.2017.1377218 -
Synergistic actions between angiotensin-converting enzyme inhibitors and statins in atherosclerosis.Nutrition, Metabolism, and... Apr 2022Hypertension and hypercholesterolemia are independent risk factors for atherosclerotic cardiovascular disease (ASCVD) by acting directly on the endothelium and... (Review)
Review
AIMS
Hypertension and hypercholesterolemia are independent risk factors for atherosclerotic cardiovascular disease (ASCVD) by acting directly on the endothelium and activating the renin-angiotensin aldosterone system (RAAS) and mevalonate pathways. This review examines how the severity and duration of these risk factors may influence the cardiovascular risk through a reciprocal interplay leading to oxidative stress and pro-inflammatory response.
DATA SYNTHESIS
The review highlights the clinical evidence supporting the benefits of statins and angiotensin-converting enzyme (ACE) inhibitors for hypertension, lipid disorders and ASCVD management, both individually and combined, at all stages of the cardiovascular continuum.
CONCLUSION
Drug strategies incorporating an ACE-inhibitor and a statin, and in particular perindopril and atorvastatin, have consistently demonstrated reductions in the rate of ASCVD events in patients with hypertension and lipid disorders, cementing their position as first-line therapies for the management of atherosclerosis complications.
Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Renin-Angiotensin System
PubMed: 35082055
DOI: 10.1016/j.numecd.2021.11.015 -
Current Cancer Drug Targets May 2011Lung cancer is a leading cause of death in both men and women, with over 1,000,000 new cases diagnosed worldwide annually and a 5-year survival rate of only 14%, a... (Review)
Review
Lung cancer is a leading cause of death in both men and women, with over 1,000,000 new cases diagnosed worldwide annually and a 5-year survival rate of only 14%, a figure that has improved little in the past thirty years. This poor prognosis suggests a need for novel approaches for the treatment and prevention of lung cancer. The renin-angiotensin system is an established, primary regulator of blood pressure, homeostasis, and natriuresis; however, compelling evidence indicates that the angiotensin peptides also play a role in cell proliferation and inflammation. Angiotensin II is a vasoconstrictor, a mitogen, and an angiogenic factor, while angiotensin-(1-7) has vasodilator, anti-proliferative, and anti-angiogenic properties. This review focuses on studies examining the renin-angiotensin system in pulmonary cancers and whether clinical intervention of this pathway may serve as an effective chemotherapeutic and/or chemopreventive modality for lung cancer.
Topics: Angiotensins; Animals; Humans; Lung Neoplasms; Peptide Fragments; Renin-Angiotensin System
PubMed: 21395552
DOI: 10.2174/156800911795538048 -
BMC Nephrology Mar 2023Hypertensive emergency is a critical disease that causes multifaceted sequelae, including end-stage kidney disease and cardiovascular disease. Although the...
BACKGROUND
Hypertensive emergency is a critical disease that causes multifaceted sequelae, including end-stage kidney disease and cardiovascular disease. Although the renin-angiotensin-aldosterone (RAA) system is enormously activated in this disease, there are few reports that attempt to characterize the effect of early use of RAA inhibitors (RASi) on the temporal course of kidney function.
METHODS
This retrospective cohort study was conducted to clarify whether the early use of RASi during hospitalization offered more favorable benefits on short-term renal function and long-term renal outcomes in patients with hypertensive emergencies. We enrolled a total of 49 patients who visited our medical center with acute severe hypertension and multiple organ dysfunction between April 2012 and August 2020. Upon admission, the patients were treated with intravenous followed by oral antihypertensive drugs, including RASi and Ca channel blockers (CCB). Kidney function as well as other laboratory and clinical parameters were compared between RASi-treated and CCB- treated group over 2 years.
RESULTS
Antihypertensive treatment effectively reduced blood pressure from 222 ± 28/142 ± 21 to 141 ± 18/87 ± 14 mmHg at 2 weeks and eGFR was gradually restored from 33.2 ± 23.3 to 40.4 ± 22.5 mL/min/1.73m at 1 year. The renal effect of antihypertensive drugs was particularly conspicuous when RASi was started in combination with other conventional antihypertensive drugs at the early period of hospitalization (2nd day [IQR: 1-5.5]) and even in patients with moderately to severely diminished eGFR (< 30 mL/min/1.73 m) on admission. In contrast, CCB modestly restored eGFR during the observation period. Furthermore, renal survival probabilities were progressively deteriorated in patients who had manifested reduced eGFR (< 15 mL/min/1.73 m) or massive proteinuria (urine protein/creatinine ≥ 3.5 g/gCr) on admission. Early use of RASi was associated with a favorable 2-year renal survival probability (0.90 [95%CI: 0.77-1.0] vs. 0.63 [95%CI: 0.34-0.92] for RASi ( +) and RASi (-), respectively, p = 0.036) whereas no apparent difference in renal survival was noted for CCB.
CONCLUSIONS
Early use of RASi contributes to the renal functional recovery from acute reduction in eGFR among patients with hypertensive emergencies. Furthermore, RASi offers more favorable effect on 2-year renal survival, compared with CCB.
Topics: Humans; Antihypertensive Agents; Renin; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Retrospective Studies; Emergencies; Kidney; Renin-Angiotensin System; Hypertension
PubMed: 36949416
DOI: 10.1186/s12882-023-03117-1 -
Basic & Clinical Pharmacology &... Sep 2021Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract, which manifest in recurring gastrointestinal inflammation. The current treatment... (Review)
Review
Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract, which manifest in recurring gastrointestinal inflammation. The current treatment options of IBD are not curative and are lacking in aspects like prevention of fibrosis. New treatment options are needed to fulfil the unmet needs and provide alternatives to drugs with resistances and side effects. Drugs targeting the renin-angiotensin system (RAS), besides being antihypertensive, also possess anti-inflammatory and antifibrotic properties and could offer an inexpensive alternative to control inflammation and fibrosis in the gut. RAS inhibitors have been effective in preventing and alleviating colitis in preclinical studies, but available human data are still sparse. This review outlines the pathophysiological functions of RAS in the gut and summarizes preclinical studies utilizing pharmacological RAS inhibitors in the treatment of experimental colitis. We discuss the alterations in intestinal RAS and the available evidence of the benefits of RAS inhibitors for IBD patients. Retrospective studies comparing IBD patients using ACE inhibitors or angiotensin II receptor blockers have provided optimistic results regarding a milder disease course and fewer hospitalizations and corticosteroid use in patients using RAS inhibitors. Prospective studies are needed to evaluate the effectiveness of these promising medications in the treatment of IBD.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Antihypertensive Agents; Colitis; Drug Evaluation, Preclinical; Fibrosis; Humans; Hypertension; Inflammation; Inflammatory Bowel Diseases; Mice; Models, Animal; Renin-Angiotensin System; Retrospective Studies
PubMed: 34128327
DOI: 10.1111/bcpt.13624 -
The International Journal of... Jun 2003The renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS) each encompasses a large number of molecules, with several participating in both systems. The... (Review)
Review
The renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS) each encompasses a large number of molecules, with several participating in both systems. The RAS generates a family of bioactive angiotensin peptides with varying biological activities. These include angiotensin-(1-8) (Ang II), angiotensin-(2-8) (Ang III), angiotensin-(3-8) (Ang IV), and angiotensin-(1-7) [Ang-(1-7)]. Ang II and Ang III act on type 1 (AT(1)) and type 2 (AT(2)) angiotensin receptors, whereas, Ang IV and Ang-(1-7) act on their own receptors. The KKS also generates a family of bioactive peptides with varying biological activities. These include hydroxylated and non-hydroxylated bradykinin and kallidin peptides and their carboxypeptidase metabolites des-Arg(9)-bradykinin and des-Arg(10)-kallidin. Whereas bradykinin and kallidin act mainly via the type 2 bradykinin (B(2)) receptor, des-Arg(9)-bradykinin and des-Arg(10)-kallidin act mainly via the type 1 bradykinin (B(1)) receptor. The AT(1) receptor forms heterodimers with the AT(2) and B(2) receptors and there is cross talk between the AT(1) and epidermal growth factor receptors. The B(2) receptor also interacts with angiotensin converting enzyme and nitric oxide synthase. Both angiotensin and kinin peptides are metabolised by many different peptidases that are important determinants of the activities of the RAS and KKS, and several of which participate in both systems.
Topics: Angiotensinogen; Angiotensins; Animals; Humans; Kallikrein-Kinin System; Receptors, Angiotensin; Renin; Renin-Angiotensin System
PubMed: 12676165
DOI: 10.1016/s1357-2725(02)00262-5 -
Physiological Reviews Apr 1961
Topics: Angiotensin Amide; Angiotensins
PubMed: 13732018
DOI: 10.1152/physrev.1961.41.2.331 -
Current Opinion in Nephrology and... Jan 2004Recent studies have reported that intrarenal angiotensin II content and angiotensin II concentrations in the proximal tubular fluid and renal interstitial fluid are much... (Review)
Review
PURPOSE OF REVIEW
Recent studies have reported that intrarenal angiotensin II content and angiotensin II concentrations in the proximal tubular fluid and renal interstitial fluid are much greater than the circulating angiotensin II levels. These high intrarenal angiotensin II levels are responsible for regulating renal hemodynamics and tubular transport.
RECENT FINDINGS
Intrarenal angiotensin II levels have been assessed from total tissue contents as well as renal interstitial fluid and proximal tubular fluid concentrations. Total tissue contents expressed per gram of tissue weight are greater than plasma angiotensin II concentrations; tubular fluid concentrations and renal interstitial fluid concentrations are even greater in the range of 3-10 pmoles/ml. In hypertensive states, there is also an increased intracellular accumulation of angiotensin II mediated by angiotensin type 1 receptor-dependent endocytosis. The high intrarenal angiotensin II levels are also caused by the presence of angiotensinogen messenger RNA and protein in the proximal tubule cells. Furthermore, there is positive amplification by which increases in circulating angiotensin II stimulate increased production and secretion of angiotensinogen, which is also manifested as an increased urinary excretion rate.
SUMMARY
The ability of the kidney to generate high intratubular and interstitial concentrations allows the kidney to regulate intrarenal levels in accord with the homeostatic needs for the regulation of renal hemodynamics and tubular reabsorption and the regulation of sodium balance. When inappropriately stimulated, high intrarenal angiotensin II levels contribute to excessive salt and water retention, the development of hypertension, and long-term proliferative effects leading to renal injury.
Topics: Angiotensin II; Angiotensins; Animals; Extracellular Fluid; Humans; Kidney; Kidney Tubules; Tissue Distribution
PubMed: 15090867
DOI: 10.1097/00041552-200401000-00015