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Drugs 1990Knowledge of the structure, function and distribution of the components of the renin-angiotensin-aldosterone system (RAS) and the integrated physiological role of this... (Review)
Review
Knowledge of the structure, function and distribution of the components of the renin-angiotensin-aldosterone system (RAS) and the integrated physiological role of this hormonal system is rapidly increasing, although many questions remain unanswered. The primary structure and localisation of RAS such as renin, prorenin, angiotensinogen, angiotensin-converting enzyme (ACE) and the angiotensins have now been described. Moreover, the genes for the production of renin and ACE have been cloned and their nucleotide sequences determined. In addition to its well-established role as a circulating endocrine system, the renin-angiotensin system has more recently been ascribed a local autocrine or paracrine function. Physiologically active levels of components such as renin and angiotensin, or their messenger RNAs, have been identified in several extrarenal tissues, notably the central nervous system. The components of such tissue renin-angiotensin systems may be derived from de novo tissue synthesis and/or from the circulation by endocytosis. Angiotensin has pharmacological actions on a wide range of body tissues, including the kidney, heart, brain, gastrointestinal tract and reproductive organs. In many of these locations, angiotensin receptors have been isolated and characterised. The most firmly established roles of angiotensin are the control of blood pressure and local blood flow, and in salt and water homeostasis; the physiological significance of many of angiotensin's tissue effects is unknown. In some areas of clinical interest, such as the pathophysiology of left ventricular hypertrophy, ACE inhibitors are very useful for elucidating the possible influences of the renin-angiotensin system.
Topics: Angiotensins; Animals; Humans; Receptors, Angiotensin; Renin-Angiotensin System
PubMed: 2407490
DOI: 10.2165/00003495-199000391-00005 -
Advances in Pharmacology (San Diego,... 2023Renin-angiotensin system (RAS) plays an indispensable role in regulating blood pressure through its effects on fluid and electrolyte balance. As an aside, cumulative...
Renin-angiotensin system (RAS) plays an indispensable role in regulating blood pressure through its effects on fluid and electrolyte balance. As an aside, cumulative evidence from experimental to clinical studies supports the notion that dysregulation of RAS contributes to the pro-inflammatory, pro-oxidative, and pro-fibrotic processes that occur in pulmonary diseases like asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute lung injury (ALI). Pharmacological intervention of the various RAS components can be a novel therapeutic strategy for the treatment of these respiratory diseases. In this chapter, we first give a recent update on the RAS, and then compile, review, and analyse recent reports on targeting RAS components as treatments for respiratory diseases. Inhibition of the pro-inflammatory renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and Ang II type 1 receptor (AT1R) axis, and activation of the protective ACE2, AT2R, Ang (1-7), and Mas receptor axis have demonstrated varying degrees of efficacies in experimental respiratory disease models or in human trials. The newly identified alamandine/Mas-related G-protein-coupled receptor member D pathway has shown some therapeutic promise as well. However, our understanding of the RAS ligand-and-receptor interactions is still inconclusive, and the modes of action and signaling cascade mediating the newly identified RAS receptors remain to be better characterized. Clinical data are obviously lacking behind the promising pre-clinical findings of certain well-established molecules targeting at different pathways of the RAS in respiratory diseases. Translational human studies should be the focus for RAS drug development in lung diseases in the next decade.
Topics: Humans; Renin-Angiotensin System; Signal Transduction; Fibrosis; Respiratory Tract Diseases; Angiotensins; Angiotensin II; Angiotensin I; Peptide Fragments; Receptor, Angiotensin, Type 1
PubMed: 37524485
DOI: 10.1016/bs.apha.2023.02.002 -
The New England Journal of Medicine Jun 1996
Review
Topics: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensins; Antihypertensive Agents; Biphenyl Compounds; Humans; Hypertension; Imidazoles; Losartan; Receptors, Angiotensin; Signal Transduction; Tetrazoles
PubMed: 8628362
DOI: 10.1056/NEJM199606203342507 -
Molecular Biotechnology May 2003Researchers continue to be fascinated with the renin-angiotensin system (RAS) more than 100 yr after its discovery because of its powerful role in controlling sodium... (Review)
Review
Researchers continue to be fascinated with the renin-angiotensin system (RAS) more than 100 yr after its discovery because of its powerful role in controlling sodium balance, body fluid volumes, and arterial pressure. Development of drugs that block different components of this system has led to powerful treatments for hypertension, heart failure, diabetes, and other diseases. Molecular approaches to studying this system offer new possibilities for better understanding the physiology and pathophysiology of the RAS, and for developing new therapeutic paradigms. Our challenge in the future will be to effectively utilize the technological advances that are taking place in virtually all areas of science, including the RAS, and to translate them into a better understanding of the pathophysiology and treatment of human diseases.
Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Blood Pressure; Hemostasis; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Hypertension; Renin-Angiotensin System
PubMed: 12721494
DOI: 10.1385/MB:24:1:27 -
The Medical Clinics of North America Jan 2004The RAAS is a powerful regulator of vascular tone and intravascular volume and of tissue architecture and a variety of other functions. The recent appreciation of the... (Review)
Review
The RAAS is a powerful regulator of vascular tone and intravascular volume and of tissue architecture and a variety of other functions. The recent appreciation of the immunoregulatory role of angiotensin II and its possible involvement in the genesis of atherosclerosis and in plaque rupture all speak to the wide-ranging physiologic and pathophysiologic activities of the peptide. So do its actions in fat cell differentiation and in neuromodulation. The system exists in the circulation, and RAASs, whole or partial, exist in many tissues. These systems are regulated at many levels ranging from the synthesis of renin to the dimerization of angiotensin receptors. Regulation occurs in multiple tissues and, as a result, tissue concentrations of angiotensin II and the concentration of other RAS components and their active metabolites can vary independently of the circulating system in these tissues. An RAS seems also to function within certain cells. Therapeutic interventions involving ACEIs and ARBs seem likely to provide benefit at least in part through the interruption of local systems. It is to be expected that with enhanced understanding of the biology of the multiple RASs, new suggestions for therapeutic interventions will be forthcoming.
Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Humans; Hypertension; Renin; Renin-Angiotensin System
PubMed: 14871049
DOI: 10.1016/s0025-7125(03)00124-x -
The American Journal of the Medical... Mar 2019Irvine Page in the United States and Eduardo Braun-Menéndez in Argentina led teams of investigators that studied the role of the kidney in blood pressure regulation....
Irvine Page in the United States and Eduardo Braun-Menéndez in Argentina led teams of investigators that studied the role of the kidney in blood pressure regulation. Contemporaneously in 1939, each team using different methods discovered and described a new substance now known as angiotensin. At the time of discovery, Page called it "angiotonin" and Braun-Menéndez called it "hipertensina," anglicized to "hypertensin." Over time, the importance of this substance in circulatory control, pathophysiology and pharmacology became indisputable and the need for a single name became obvious. In a remarkable accommodation, Page and Braun-Menéndez agreed to forego any claim to priority and chose a name with elements of both. Following this compromise, Page and Braun-Menéndez went on to become leaders in science in their own countries as well as recognition world-wide while, angiotensin and its derivatives have become standard components in the understanding and treatment of diseases of the heart, kidney and brain.
Topics: Angiotensins; Argentina; Blood Circulation; Blood Pressure; History, 20th Century; Humans; International Cooperation; Kidney; United States
PubMed: 30798942
DOI: 10.1016/j.amjms.2018.08.017 -
Bruxelles Medical Jan 1965
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Hypertension Research : Official... Jun 2011Angiotensin (Ang) II, the main effector peptide of the renin-Ang system, increases arterial blood pressure through Ang II type 1A (AT(1a)) receptor-dependent arterial... (Review)
Review
Angiotensin (Ang) II, the main effector peptide of the renin-Ang system, increases arterial blood pressure through Ang II type 1A (AT(1a)) receptor-dependent arterial vasoconstriction and by decreasing renal salt and water excretion through extrarenal and intrarenal mechanisms. AT(2) receptors are assumed to oppose these responses mediated by AT(1) receptors, thereby attenuating the pressor effects of Ang II. Nevertheless, a possible role of AT(2) receptors in the regulation of renal hemodynamics and sodium homeostasis remains to be unclear. Several other Ang fragments such as Ang III, Ang IV, Ang-(1-7) and Ang A have also been shown to display biological activity. In this review, we focus on the effects of these Ang on blood pressure, renal hemodynamics and sodium water handling, and discuss the receptors involved in these actions.
Topics: Angiotensin II; Angiotensin III; Angiotensins; Animals; Blood Pressure; Hemodynamics; Humans; Kidney; Peptide Fragments; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renal Circulation; Sodium
PubMed: 21412242
DOI: 10.1038/hr.2011.24 -
Journal of Cardiothoracic and Vascular... Apr 2008
Topics: Anesthesia, General; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Humans; Risk Factors
PubMed: 18375316
DOI: 10.1053/j.jvca.2008.01.002 -
Comparative Biochemistry and... Jan 2001In mammals, a principal bioactive component of the renin-angiotensin system (RAS), angiotensin II (ANG II), is known to be vasopressor, dipsogenic, a stimulant of... (Review)
Review
In mammals, a principal bioactive component of the renin-angiotensin system (RAS), angiotensin II (ANG II), is known to be vasopressor, dipsogenic, a stimulant of adrenocortical secretion and to control glomerular and renal tubular function. Historically, a RAS analogous to that found in mammals was thought to have first evolved in the bony fishes. Recent research has identified the unusually structured elasmobranch [Asp(1)-Pro(3)-Ile(5)] ANG II. Physiological studies have demonstrated that ANG II in elasmobranchs is vasopressor, and stimulates interrenal gland production of the elasmobranch corticosteroid 1alpha-hydroxycorticosterone. The specific binding of ANG II in elasmobranchs has been reported in gills, heart, interrenal gland, gut and rectal gland. The precise osmoregulatory role ANG II plays in cartilaginous fishes is not yet known; however, putative evidence is emerging for a role in the control of drinking rate, rectal gland secretion, and kidney function.
Topics: Adrenal Cortex; Amino Acid Sequence; Angiotensins; Animals; Cardiovascular Physiological Phenomena; Elasmobranchii; Receptors, Angiotensin; Renin-Angiotensin System; Water-Electrolyte Balance
PubMed: 11137437
DOI: 10.1016/s1095-6433(00)00295-6