Angiotensin

Information about Angiotensin


Space-filling models of angiotensin I (left) and II (right). From PDB 1N9U and 1N9V.
Angiotensinogen
Identifiers
Symbol	AGT
Entrez	183
HUGO	333
OMIM	106150
RefSeq	&rn=1 NM_000029
UniProt	P01019
Other data
Locus	Chr. 1 q41-qter

Angiotensin is an oligopeptide in the blood that causes vasoconstriction, increased blood pressure, and release of aldosterone from the adrenal cortex. It is a powerful dipsogen. It is derived from the precursor molecule angiotensinogen, a serum globulin produced in the liver. It plays an important role in the renin-angiotensin system. Angiotensin was first isolated at the Cleveland Clinic.

Precursor, and types of angiotensin

Angiotensinogen

Angiotensinogen is an α-2-globulin that is produced constitutively and released into the circulation mainly by the liver. It is a member of the serpin family, although it is not known to inhibit other enzymes, unlike most serpins. Plasma angiotensinogen levels are increased by plasma corticosteroid, estrogen, thyroid hormone, and angiotensin II levels.

Angiotensinogen consist of 453 amino acid residues.

Angiotensin I

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu

Renin-angiotensin-aldosterone system

Angiotensin I (CAS# 11128-99-7) is formed by the action of renin on angiotensinogen. Renin is produced in the kidneys in response to both decreased intra-renal blood pressure at the juxtaglomerular cells, or decreased delivery of Na+ and Cl- to the macula densa. If more Na+ is sensed, renin release is decreased.

Renin cleaves the peptide bond between the leucine (Leu) and valine (Val) residues on angiotensinogen, creating the ten amino acid peptide (des-Asp) angiotensin I (CAS# 9041-90-1).

Angiotensin I appears to have no biological activity and exists solely as a precursor to angiotensin II.

Angiotensin II

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe | His-Leu

Angiotensin I is converted to angiotensin II through removal of two terminal residues by the enzyme Angiotensin-converting enzyme (ACE, or kininase), which is found predominantly in the capillaries of the lung.^[1] Angiotensin II acts as an endocrine, autocrine/ paracrine, and intracrine hormone.

ACE is a target for inactivation by ACE inhibitor drugs, which decrease the rate of angiotensin II production. Other cleavage products, 7 or 9 amino acids long, are also known; they have differential affinity for angiotensin receptors, although their exact role is still unclear. The action of angiotensin II itself is targeted by angiotensin II receptor antagonists, which directly block angiotensin II AT₁ receptors.

Angiotensin II is degraded to angiotensin III by angiotensinases that are located in red blood cells and the vascular beds of most tissues. It has a half-life in circulation of around 30 seconds, while in tissue, it may be as long as 15-30 minutes.

Angiotensin III

Asp | Arg-Val-Tyr-Ile-His-Pro-Phe

Angiotensin III has 40% of the pressor activity of Angiotensin II, but 100% of the aldosterone-producing activity.

Angiotensin IV

Arg | Val-Tyr-Ile-His-Pro-Phe

Angiotensin IV is a hexapeptide which, like angiotensin III, has some lesser activity.

Effects of angiotensin

See also Renin-angiotensin_system#Effects

Angiotensins II, III & IV have a number of effects throughout the body:

Cardiovascular effects

It is a potent direct vasoconstrictor, constricting arteries and veins and increasing blood pressure.

Angiotensin II has prothrombotic potential through adhesion and aggregation of platelets and production of PAI-1 and PAI-2.^[2]^[3]

It has been proposed that angiotensin II could be a cause of vascular and cardiac muscle hypertrophy (enlargement of the heart).

Neural effects

Angiotensin II increases thirst sensation (dipsogen) through the subfornical organ (SFO) of the brain, decreases the response of the baroreceptor reflex, and increases the desire for salt. It increases secretion of ADH in the posterior pituitary and secretion of ACTH in the anterior pituitary. It also potentiates the release of norepinephrine by direct action on postganglionic sympathetic fibers.

Adrenal effects

Angiotensin II acts on the adrenal cortex, causing it to release aldosterone, a hormone that causes the kidneys to retain sodium and lose potassium. Elevated plasma angiotensin II levels are responsible for the elevated aldosterone levels present during the luteal phase of the menstrual cycle.

Renal effects

Angiotensin II has a direct effect on the proximal tubules to increase Na⁺ resorption. Although it slightly inhibits glomerular filtration by indirectly (through sympathetic effects) and directly stimulating mesangial cell constriction, its overall effect is to increase the glomerular filtration rate by increasing the renal perfusion pressure via efferent renal arteriole constriction. Angiotensin II causes the release of prostaglandins from the kidneys.

References

1. ^ Physiology at MCG 7/7ch09/7ch09p16
2. ^ Skurk T, Lee YM,Hauner H. "Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture." Hypertension. 2001 May;37(5):1336-40. PMID 11358950
3. ^ Gesualdo L, et al. "Angiotensin IV stimulates plasminogen activator inhibitor-1 expression in proximal tubular epithelial cells." Kidney Int. 1999 Aug;56(2):461-70. PMID 10432384

Brenner & Rector's The Kidney, 7th ed., Saunders, 2004.
Mosby's Medical Dictionary, 3rd Ed., CV Mosby Company, 1990.
Review of Medical Physiology, 20th Ed., William F. Ganong, McGraw-Hill, 2001.

External links

MeSH Angiotensins

• • [ e] Cardiovascular system, physiology: cardiovascular physiology
Volumes	Preload - Afterload - End-systolic volume - End-diastolic volume - Frank-Starling law of the heart
Interactions	Cardiac output - Wiggers diagram - Pressure volume diagram
Tropism	Chronotropic - Dromotropic - Inotropic
Hemodynamics	Baroreflex - Kinin-kallikrein system - Renin-angiotensin system - Vasoconstrictors - Vasodilators - Compliance - Vascular resistance
Other	Electrical conduction system of the heart (Cardiac action potential)

• • [ e] Peptides: neuropeptides
Hypothalamic	Somatostatin - CRH - GnRH - GHRH - Orexins - TRH - POMC (ACTH, MSH, Lipotropin)
Gastrointestinal hormones	Cholecystokinin - Gastric inhibitory polypeptide - Gastrin - Motilin - Secretin - Vasoactive intestinal peptide
Other hormones	Vasopressin - Calcitonin -
Other	Angiotensin - Bombesin/Neuromedin B - Calcitonin gene-related peptide - Carnosine - Delta sleep-inducing peptide - FMRFamide - Galanin - Gastrin releasing peptide - Kinins (Bradykinin, Tachykinins ) - Neuromedin (B, N, U) - Neuropeptide Y - Neurophysins - Neurotensin - Opioid peptide - Pancreatic polypeptide - Pituitary adenylate cyclase activating peptide

• • [ e] Autacoids
Angiotensin - Eicosanoid - Histamine - Kinin - Platelet-activating factor - Serotonin

Space-filling models (also known as calotte models or CPK models^[1] by Corey, Pauling and Koltun), like ball-and-stick models, belong to the 3D or spatial molecular models, which serve to display the structure of chemical products and substances or
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Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. This data, typically obtained by X-ray crystallography or NMR spectroscopy, is submitted by biologists and biochemists from around the world, is released into the public domain,
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The Entrez Global Query Cross-Database Search System is a powerful federated search engine, or web portal that allows users to search many discrete health sciences databases at the National Center for Biotechnology Information (NCBI) website.
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Hugo is a male given name, a latinized form of the name Hugh, a German/Teutonic name meaning "Bright in Mind and Spirit".

Hugo is one of the most popular names in Europe ranking as high as #2 in France, #6 in Spain, and #7 in Belgium in 2006.
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The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988.
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Swiss-Prot is a manually curated biological database of protein sequences. Swiss-Prot was created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute.
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locus (plural loci) is a fixed position on a chromosome, such as the position of a gene or a biomarker (genetic marker). A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map.
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Peptides (from the Greek πεπτίδια, "small digestibles") are short polymers formed from the linking, in a defined order, of α-amino acids.
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Blood is a specialized biological fluid consisting of red blood cells (also called RBCs or erythrocytes), white blood cells (also called leukocytes) and platelets (also called thrombocytes) suspended in a complex fluid medium known as blood plasma.
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Vasoconstriction is a narrowing of the lumen of blood vessels.

Factors

Factors that trigger vasoconstriction are both of exogenous origin, i.e. medication, and as a response from the body itself.

Body mechanisms

Vasoconstriction is a procedure of the body to e.g.
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Blood pressure (strictly speaking: vascular pressure) refers to the force exerted by circulating blood on the walls of blood vessels, and constitutes one of the principal vital signs.
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Aldosterone is a steroid hormone (mineralocorticoid family) produced by the outer-section (zona glomerulosa) of the adrenal cortex in the adrenal gland to regulate sodium and potassium balance in the blood.

It was first isolated by Simpson and Tait in 1953.
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adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.
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Definition

A dipsogen is an agent that causes thirst. (From Greek: dypsa: thirst and the suffix -gen, to create.)

Physiology

Angiotensin II is thought to be a powerful dipsogen, and is one of the products of the renin-angiotensin pathway, a biological
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liver is an organ present in vertebrates and some other animals. It plays a major role in metabolism and has a number of functions in the body, including glycogen storage, decomposition of red blood cells, plasma protein synthesis, and detoxification.
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For an autonomous region of Nicaragua, see .

The renin-angiotensin system (RAS) or the renin-angiotensin-aldosterone system (RAAS) is a hormone system that helps regulate long-term blood pressure and extracellular volume in the body.
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Cleveland Clinic

Location
Place Cleveland, Ohio, (USA)

Organisation
Care System Private
Hospital Type Academic
Affiliated University
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Alpha Globulins are a group of globular proteins in plasma, which are highly mobile in alkaline or electrically charged solutions. They inhibit certain blood protease and inhibitor activity.
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Serpins are a group of proteins with similar structures that were first identified as a set of proteins able to inhibit proteases. The name serpin is derived from this activity - serine protease inhibitors.
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Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood
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Estrogens (alternative spellings: oestrogens or œstrogens) are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone.
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For other uses, see Thyroid cartilage.

The thyroid is one of the largest endocrine glands in the body. This gland is found in the neck just below the laryngeal prominence.
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hormone (from Greek όρμή - "to set in motion") is a chemical messenger that carries a signal from one cell (or group of cells) to another. All multicellular organisms produce hormones (including plants - see phytohormone).
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amino acid is a molecule that contains both amine and carboxyl functional groups. In biochemistry, this term refers to alpha-amino acids with the general formula H₂NCHRCOOH, where R is an organic substituent.
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CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. They are also referred to as CAS numbers, CAS RNs or CAS #s.
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Renin (pronounced "Ree-nin" or "Rē-nin" (IPA: /ˈriːnɨn/)), also known as angiotensinogenase
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The kidneys are organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. The medical field that studies the kidneys and diseases of the kidney is called nephrology^[1].
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In the kidney, the juxtaglomerular cells (JG cells, also known as granular cells) are cells that synthesize, store, and secrete the enzyme renin. They are specialized smooth muscle cells in the wall of the afferent arteriole that delivers blood to the glomerulus.
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In the kidney, the macula densa is an area of closely packed specialized cells lining the region of the distal convoluted tubule (DCT) lying next to the glomerular vascular pole.
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