Angiotensinogen (serpin peptidase inhibitor, clade A, member 8)
Space-filling models of angiotensin I (left) and II (right). Space-filling models (also known as calotte models or CPK models by Corey, Pauling and Koltun like Ball-and-stick models belong From PDB 1N9U and 1N9V. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography
Identifiers
Symbol(s)	AGT; ANHU; SERPINA8
External IDs	OMIM: 106150 MGI: 87963 HomoloGene: 14
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	183	11606
Ensembl	ENSG00000135744	ENSMUSG00000031980
Uniprot	P01019	Q3UTR7
Refseq	NM_000029 (mRNA) NP_000020 (protein)	NM_007428 (mRNA) NP_031454 (protein)
Location	Chr 1: 228.9 - 228.92 Mb	Chr 8: 127.44 - 127.46 Mb
Pubmed search	[1]	[2]

Angiotensin causes blood vessels to constrict, and drives blood pressure up. The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mouse Genome Informatics (MGI website is run by The Jackson Laboratory. HomoloGene, a tool of the National Center for Biotechnology Information (NCBI is a system for automated detection of homologs (similarity attributable to descent 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 Ensembl is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent UniProt is the uni versal prot ein resource a central repository of Protein data created by combining Swiss-Prot, TrEMBL PubMed is a free search engine for accessing the MEDLINE database of citations and abstracts of biomedical research articles It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. The renin-angiotensin system (RAS or the renin-angiotensin-aldosterone system (RAAS is a hormone system that regulates Blood pressure and water ( fluid Angiotensin also creates aldosterone, which causes the tubules of the kidneys to retain sodium and water, which also drives blood pressure up.

Angiotensin is an oligopeptide in the blood that causes vasoconstriction, increased blood pressure, and release of aldosterone from the adrenal cortex. Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells ��such as nutrients and oxygen—and transports Waste products Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels particularly the large Arteries, Arterioles Blood pressure is also the title of a short story by Damon Runyan in Guys and Dolls and Other Stories Aldosterone is a hormone that causes the tubules of the kidneys to retain sodium and water Situated along the perimeter of the Adrenal gland, the adrenal cortex mediates the stress response through the production of Mineralocorticoids and Glucocorticoids It is a hormone and a powerful dipsogen. Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body A dipsogen is an agent that causes Thirst. (From Greek dypsa, "thirst" and the suffix -gen, "to create" It is derived from the precursor molecule angiotensinogen, a serum globulin produced in the liver. The liver is a vital organ in the human body and is present in Vertebrates and some other animals It plays an important role in the renin-angiotensin system. The renin-angiotensin system (RAS or the renin-angiotensin-aldosterone system (RAAS is a hormone system that regulates Blood pressure and water ( fluid Angiotensin was independently isolated in Indianapolis and Argentina in the late 1930s (as 'Angiotonin' and 'Hypertensin' respectively) and subsequently characterised and synthesized by groups at the Cleveland Clinic and Ciba laboratories in Basel, Switzerland. The Cleveland Clinic (formally known as the Cleveland Clinic Foundation) is a multispecialty academic medical center located in Cleveland, Ohio, Ciba is a Chemical company based in and near Basel, Switzerland. ^[1]

Contents 1 Precursor, and types of angiotensin 1.1 Angiotensinogen 1.2 Angiotensin I 1.3 Angiotensin II 1.4 Angiotensin III 1.5 Angiotensin IV 2 Effects 2.1 Cardiovascular effects 2.2 Neural effects 2.3 Adrenal effects 2.4 Renal effects 3 See also 4 References 5 Further reading 6 External links

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. Alpha Globulins are a group of Globular proteins in plasma, which are highly mobile in Alkaline or electrically charged solutions It is a member of the serpin family, although it is not known to inhibit other enzymes, unlike most serpins. 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 Plasma angiotensinogen levels are increased by plasma corticosteroid, estrogen, thyroid hormone, and angiotensin II levels. Corticosteroids are a class of Steroid hormones that are produced in the Adrenal cortex. Estrogens (US otherwise oestrogens or œstrogens) are a group of Steroid compounds named for their importance in the Estrous cycle, The thyroid is one of the largest Endocrine glands in the body Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body

Angiotensinogen is also known as renin substrate.

Human angiotensinogen is 118 amino acids long, but other species have angiotensinogen of varying sizes^[2]

Angiotensin I

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

Angiotensin I (CAS# 11128-99-7) is formed by the action of renin on angiotensinogen. The renin-angiotensin system (RAS or the renin-angiotensin-aldosterone system (RAAS is a hormone system that regulates Blood pressure and water ( fluid CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to Renin (pronounced "Ree-nin" or "Rē-nin" (ˈriːnɨn also known as Angiotensinogenase, is a circulating Enzyme that participates in the body's Angiotensin causes blood vessels to constrict and drives blood pressure up 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. The kidneys are complicated organs that have numerous biological roles In the Kidney, the juxtaglomerular cells ( JG cells, also known as granular cells) are cells that synthesize store and secrete the enzyme Renin In the Kidney, the macula densa is an area of closely packed specialized cells lining the wall of the Distal convoluted tubule (DCT at the point of return 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). A peptide bond is a Chemical bond formed between two Molecules when the Carboxyl group of one molecule reacts with the Leucine (abbreviated as Leu or L) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH2CH(CH32 Valine (abbreviated as Val or V) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH(CH32 In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to

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 kinase), which is found predominantly in the capillaries of the lung. Angiotensin I converting enzyme ( ACE,) is an Exopeptidase. Functions It has two primary functions it catalyses the conversion of Capillaries are the smallest of a body's Blood vessels measuring 5-10 μm in diameter which connect Arterioles and Venules and enable the interchange ^[3] ACE is actually found all over the body, but has its highest density in the lung due to the high density of capillary beds there. Angiotensin II acts as an endocrine, autocrine/ paracrine, and intracrine hormone. The endocrine system is an integrated system of small organs that involve the release of extracellular signaling molecules known as Hormones The endocrine system is instrumental Autocrine signaling is a form of signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent that binds to autocrine receptors on the same cell leading Paracrine signaling is a form of Cell signaling in which the target cell is near (" Para " = near the signal-releasing cell Intracrine refers to a Hormone that acts inside a cell. Steroid hormones act through intracellular (mostly nuclear receptors and are thus considered as

ACE is a target for inactivation by ACE inhibitor drugs, which decrease the rate of angiotensin II production. ACE inhibitors, or inhibitors of '''A'''ngiotensin-'''C'''onverting '''E'''nzyme, are a group of Pharmaceuticals that are used primarily in treatment of Hypertension Angiotensin II increases blood pressure by stimulating the Gq protein in vascular smooth muscle cells (which in turn activates contraction by an IP3-dependent mechanism). ACE inhibitor drugs are major drugs against hypertension. ACE inhibitors, or inhibitors of '''A'''ngiotensin-'''C'''onverting '''E'''nzyme, are a group of Pharmaceuticals that are used primarily in treatment of Hypertension

Other cleavage products of ACE, 7 or 9 amino acids long, are also known; they have differential affinity for angiotensin receptors, although their exact role is still unclear. The angiotensin receptors are a class of G protein-coupled receptors with Angiotensins as ligands They are important in the Renin-angiotensin system The action of angiotensin II itself is targeted by angiotensin II receptor antagonists, which directly block angiotensin II AT₁ receptors. Angiotensin II receptor antagonists, also known as angiotensin receptor blockers (ARBs AT1-receptor antagonists or sartans, are a group of The angiotensin receptors are a class of G protein-coupled receptors with Angiotensins as ligands They are important in the Renin-angiotensin system

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. Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels particularly the large Arteries, Arterioles

Angiotensin IV

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

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

Effects

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. The renin-angiotensin system (RAS or the renin-angiotensin-aldosterone system (RAAS is a hormone system that regulates Blood pressure and water ( fluid Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels particularly the large Arteries, Arterioles

Angiotensin II has prothrombotic potential through adhesion and aggregation of platelets and production of PAI-1 and PAI-2. Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved Plasminogen activator inhibitor-1 is the principal inhibitor of Tissue plasminogen activator (tPA and Urokinase (uPA the activators of Plasminogen Plasminogen activator inhibitor-2 (placental PAI is a Coagulation factor that inactivates TPA and Urokinase. ^[4][5]

When cardiac cell growth is stimulated, a local (autocrine-paracrine) renin-angiotensin system is activated in the cardiac myocte, which stimulates cardiac cell growth through Protein Kinase C. The same system can be activated in smooth muscle cells in conditions of hypertension, atherosclerosis or endothelial damage. Angiotensin II is the most important Gq stimulator of the heart during hypertrophy, compared to endothelin-1 and A1 adrenoreceptors.

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. Thirst is the craving for liquids resulting in the basic Instinct of humans or animals to Drink. A dipsogen is an agent that causes Thirst. (From Greek dypsa, "thirst" and the suffix -gen, "to create" The subfornical organ, situated on the ventral surface of the fornix, at the Foramen of Monro, is one of the Circumventricular organs of the Brain In Cardiovascular physiology, the baroreflex or baroreceptor reflex is one of the body's homeostatic mechanisms for maintaining Blood pressure Salt is a Dietary mineral composed primarily of Sodium chloride that is essential for Animal life but toxic to most land plants It increases secretion of ADH in the posterior pituitary and secretion of ACTH in the anterior pituitary. Arginine vasopressin ( AVP) also known as vasopressin, argipressin or antidiuretic hormone ( ADH) is a Hormone found in The posterior pituitary (or neurohypophysis) comprises the Posterior lobe of the Pituitary gland and is part of the Endocrine system. Adrenocorticotropic hormone ( ACTH or corticotropin) is a Polypeptide Hormone produced and secreted by the Pituitary gland It also potentiates the release of norepinephrine by direct action on postganglionic sympathetic fibers. Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a The Sympathetic Nervous System ( SNS) is a branch of the Autonomic nervous system along with the Enteric nervous system and Parasympathetic nervous

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. Situated along the perimeter of the Adrenal gland, the adrenal cortex mediates the stress response through the production of Mineralocorticoids and Glucocorticoids Aldosterone is a hormone that causes the tubules of the kidneys to retain sodium and water Elevated plasma angiotensin II levels are responsible for the elevated aldosterone levels present during the luteal phase of the menstrual cycle. The menstrual cycle is a recurring cycle of physiologic changes that occurs in reproductive-age Females Overt menstruation (where there is blood flow from the

Renal effects

Angiotensin II has a direct effect on the proximal tubules to increase Na⁺ absorption. It has a complex and variable effect on glomerular filtration and renal blood flow depending on the setting. Renal function, in Nephrology, is an indication of the state of the Kidney and its role in Renal physiology. In the physiology of the Kidney, renal blood flow ( RBF) is the volume of Blood delivered to the kidneys per unit time Increases in systemic blood pressure will maintain renal perfusion pressure, however constriction of the afferent and efferent glomerular arterioles will tend to restrict renal blood flow. The effect on the efferent arteriolar resistance is, however, markedly greater, in part due to its smaller basal diameter; this tends to increase glomerular capillary hydrostat pressure and maintain glomerular filtration rate. Renal function, in Nephrology, is an indication of the state of the Kidney and its role in Renal physiology. A number of other mechanism can affect renal blood flow and GFR. High concentrations of Angiotensin II can constrict the glomerular mesangium reducing the area for glomerular filtration. Angiotensin II as a a sensitizer to Tubuloglomerular feedback preventing an excessive rise in GFR. In the physiology of the kidney, tubuloglomerular feedback ( TGF) is one of several mechanisms the kidney uses to regulate Glomerular filtration rate (GFR Angiotensin II causes the local release of prostaglandins which in turn antagonize renal vasoconstriction. The net effect of these completing mechanisms on glomerular filtration will vary with the physiological and pharmaclogical environment.

Renal effects of Angiotensin II

Target	Action	Mechanism[6]
Renal artery & afferent arterioles	vasoconstriction	VDCCs --> Ca2+ influx
efferent arteriole	vasoconstriction	(probably) activate Angiotensin receptor 1 --> Activation of Gq --> ↑PLC activity --> ↑IP3 and DAG --> activation of IP3 receptor in SR --> ↑intracellular Ca2+
mesangial cells	contraction --> ↓filtration area	activation of Gq --> ↑PLC activity --> ↑IP3 and DAG --> activation of IP3 receptor in SR --> ↑intracellular Ca2+ VDCCs --> Ca2+ influx
Tubuloglomerular feedback	Increased sensitivity	Responsiveness increase of afferent arteriole to signals from macula densa
medullary blood flow	Reduction

See also

• ACE inhibitor
• Angiotensin receptor
• Angiotensin II receptor antagonist

References

Further reading

External links

• MeSH Angiotensins

Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books

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