WordNet

the 9th letter of the Roman alphabet (同)i
any of several vasoconstrictor substances (trade name Hypertensin) that cause narrowing of blood vessels (同)angiotonin, Hypertensin

PrepTutorEJDIC

『私は』私が
iodineの化学記号

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/27 14:41:52」(JST)

wiki en

Angiotensin is a peptide hormone that causes vasoconstriction and a subsequent increase in blood pressure. It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone, from the adrenal cortex. Aldosterone promotes sodium retention in the distal nephron, in the kidney, which also drives blood pressure up.

Angiotensin is an oligopeptide and is a hormone and 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 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.^[1]

Precursor, and types of angiotensin

Angiotensinogen

Angiotensinogen is an α-2-globulin 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 is also known as renin substrate. Human angiotensinogen is 453 amino acids long, but other species have angiotensinogen of varying sizes. The first 12 amino acids are the most important for activity.

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

Angiotensin I

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

Renin–angiotensin–aldosterone system

Angiotensin I (CAS# 11128-99-7) is formed by the action of renin on angiotensinogen. 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. Renin is produced in the kidneys in response to renal sympathetic activity, decreased intrarenal blood pressure (<90mmHg systolic blood pressure^[2] ) at the juxtaglomerular cells, or decreased delivery of Na+ and Cl- to the macula densa.^[3] If less Na+ is sensed by the macula densa, renin release by juxtaglomerular cells is increased.

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 (AII) through removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE), primarily through ACE within the lung (but also present in endothelial cells and kidney epithelial cells). ACE found in other tissues of the body has no physiological role (ACE has a high density in the lung, but activation here promotes no vasoconstriction, angiotensin II is below physiological levels of action).^{[citation needed]} 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. Angiotensin II increases blood pressure by stimulating the Gq protein in vascular smooth muscle cells (which in turn activates an IP3-dependent mechanism leading to a rise in intracellular calcium levels and ultimately causing contraction). In addition, angiotensin II acts at the Na/H exchanger in the proximal tubules of the kidney to stimulate Na reabsorption and H excretion which is coupled to bicarbonate reabsorption. This ultimately results in an increase in blood volume, pressure, and pH.^[4] Hence, ACE inhibitors are major anti-hypertensive drugs.

Other cleavage products of ACE, seven 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 AII itself is targeted by angiotensin II receptor antagonists, which directly block angiotensin II AT₁ receptors.

Angiotensin II is degraded to angiotensin III by angiotensinases located in red blood cells and the vascular beds of most tissues. It has a half-life in circulation of around 30 seconds, whereas, 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. Increases mean arterial pressure.

Angiotensin IV

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

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

Effects

See also Renin-angiotensin system#Effects

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

Adipic

Angiotensins "modulate fat mass expansion through upregulation of adipose tissue lipogenesis ... and downregulation of lipolysis " ^[5]

Cardiovascular

They are potent direct vasoconstrictors, constricting arteries and veins and increasing blood pressure. This effect is achieved through activation of the GCPR AT1, which signals through a Gq protein to activate Phospholipase C, and subsequently increase intracellular calcium.^[6]

Angiotensin II has prothrombotic potential through adhesion and aggregation of platelets and stimulation of PAI-1 and PAI-2.^[7]^[8]

When cardiac cell growth is stimulated, a local (autocrine-paracrine) renin-angiotensin system is activated in the cardiac myocyte, 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 α1 adrenoreceptors.^{[citation needed]}

Neural

Angiotensin II increases thirst sensation (dipsogen) through the subfornical organ 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

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

Angiotensin II has a direct effect on the proximal tubules to increase Na⁺ reabsorption. It has a complex and variable effect on glomerular filtration and renal blood flow depending on the setting. 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 hydrostatic pressure and maintain glomerular filtration rate. A number of other mechanisms 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 is a sensitizer to tubuloglomerular feedback, preventing an excessive rise in GFR. Angiotensin II causes the local release of prostaglandins, which, in turn, antagonize renal vasoconstriction. The net effect of these competing mechanisms on glomerular filtration will vary with the physiological and pharmacological environment.

Direct Renal effects of angiotensin II (not including aldosterone release)
Target	Action	Mechanism^[9]
renal artery & afferent arterioles	vasoconstriction (weaker)	VDCCs → Ca²⁺ influx
efferent arteriole	vasoconstriction (stronger)	(probably) activate Angiotensin receptor 1 → Activation of G_q → ↑PLC activity → ↑IP₃ and DAG → activation of IP₃ receptor in SR → ↑intracellular Ca²⁺
mesangial cells	contraction → ↓filtration area	activation of G_q → ↑PLC activity → ↑IP₃ and DAG → activation of IP₃ receptor in SR → ↑intracellular Ca²⁺ VDCCs → Ca²⁺ influx
proximal tubule	increased Na⁺ reabsorption	adjustment of Starling forces in peritubular capillaries to favour increased reabsorption efferent and afferent arteriole contraction → decreased hydrostatic pressure in peritubular capillaries efferent arteriole contraction → increased filtration fraction → increased colloid osmotic pressure in peritubular capillaries increased sodium–hydrogen antiporter activity
tubuloglomerular feedback	increased sensitivity	increase in afferent arteriole responsiveness to signals from macula densa
medullary blood flow	reduction

References

^ Basso N, Terragno NA (Dec 2001). "History about the discovery of the renin-angiotensin system". Hypertension 38 (6): 1246–9. doi:10.1161/hy1201.101214. PMID 11751697.
^ "JAMA Article Jan 2012".
^ Williams GH, Dluhy RG (2008). "Chapter 336: Disorders of the Adrenal Cortex". In Loscalzo J, Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL. Harrison's principles of internal medicine. McGraw-Hill Medical. ISBN 0-07-146633-9.
^ Le, Tao (2012). First Aid for the Basic Sciences. Organ Systems. McGraw-Hill. p. 625.
^ Yvan-Charvet L, Quignard-Boulangé A (Jan 2011). "Role of adipose tissue renin-angiotensin system in metabolic and inflammatory diseases associated with obesity". Kidney International 79 (2): 162–8. doi:10.1038/ki.2010.391. PMID 20944545.
^ Kanaide, Hideo; Ichiki, Toshihiro; Nishimura, Junji; Hirano, Katsuya (2003-11-28). "Cellular Mechanism of Vasoconstriction Induced by Angiotensin II It Remains To Be Determined". Circulation Research 93 (11): 1015–1017. doi:10.1161/01.RES.0000105920.33926.60. ISSN 0009-7330. PMID 14645130.
^ Skurk T, Lee YM, Hauner H (May 2001). "Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture". Hypertension 37 (5): 1336–40. doi:10.1161/01.HYP.37.5.1336. PMID 11358950.
^ Gesualdo L, Ranieri E, Monno R, Rossiello MR, Colucci M, Semeraro N, Grandaliano G, Schena FP, Ursi M, Cerullo G (Aug 1999). "Angiotensin IV stimulates plasminogen activator inhibitor-1 expression in proximal tubular epithelial cells". Kidney International 56 (2): 461–70. doi:10.1046/j.1523-1755.1999.00578.x. PMID 10432384.
^ Boulpaep EL, Boron WF (2005). Medical Physiology: a Cellular and Molecular Approach. St. Louis, Mo: Elsevier Saunders. p. 771. ISBN 1-4160-2328-3.

External links

The MEROPS online database for peptidases and their inhibitors: I04.953
Angiotensins at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 急性心筋梗塞におけるアンギオテンシン変換酵素阻害剤およびアンギオテンシン受容体遮断剤：使用の推奨 angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction recommendations for use
2. 心不全におけるアンギオテンシン変換酵素阻害剤およびアンギオテンシン受容体拮抗剤：作用機序 angiotensin converting enzyme inhibitors and receptor blockers in heart failure mechanisms of action
3. 心臓におけるアンギオテンシンⅡの作用 actions of angiotensin ii on the heart
4. 高血圧治療におけるレニン・アンギオテンシン系阻害 renin angiotensin system inhibition in the treatment of hypertension
5. Chapter 2B：レニン－アンギオテンシン系 chapter 2b renin angiotensin system

English Journal

Cardiovascular ultrasound exploration contributes to predict incident atrial fibrillation in arterial hypertension: The Campania Salute Network.

Losi MA1, Izzo R2, De Marco M2, Canciello G1, Rapacciuolo A1, Trimarco V3, Stabile E1, Rozza F2, Esposito G1, De Luca N2, de Simone G4, Trimarco B1.
International journal of cardiology.Int J Cardiol.2015 Nov 15;199:290-5. doi: 10.1016/j.ijcard.2015.07.019. Epub 2015 Jul 12.
BACKGROUND: Interaction of cardiovascular (CV) risk factors with structural and hemodynamic alterations as combined promoters of atrial fibrillation (AF) is not yet well studied. We designed an observational, longitudinal, retrospective study to predict risk of incident AF by combination of CV risk
PMID 26218588

Effects of neonatal inflammation on the inflammatory and oxidative profile during experimental sepsis in adult life.

Lunardelli A1, Luft C2, Pedrazza L1, Martha BA1, de Oliveira JR1, Donadio MV3.
Physiology & behavior.Physiol Behav.2015 Nov 1;151:516-24. doi: 10.1016/j.physbeh.2015.08.023. Epub 2015 Aug 24.
The present study aimed to evaluate the long-term effects of neonatal inflammation on the inflammatory and oxidative profile during experimental sepsis in adult life. Neonatal Balb/c mice received different treatments on day 10: LPS i.p. injection (100g/kg) (nLPS) or saline i.p. injection (nSal). As
PMID 26314499

Japanese Journal

III．治療のポイント―生活習慣の修正と降圧薬治療

日本内科学会雑誌 104(2), 218-231, 2015
NAID 130005125511

Zone Sharpening of Peptides in Pressurized Capillary Electrochromatography Using Dynamic pH Junction

Analytical Sciences 31(11), 1151-1154, 2015
NAID 130005108610

術前管理に苦慮した肺結核併存原発性アルドステロン症の1例

日本臨床外科学会雑誌 75(12), 3348-3353, 2014
NAID 130005085350

Related Pictures

★リンクテーブル★

リンク元	「アンギオテンシンIII」
関連記事	「II」「I」「angiotensin」

「アンギオテンシンIII」

Angiotensinogen (serpin peptidase inhibitor, clade A, member 8)
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1N9U, 1N9V, 2JP8, 2WXW, 2X0B, 3CK0, 3WOO, 3WOR, 4AA1, 4APH, 4FYS
Identifiers
Symbols	AGT ; ANHU; SERPINA8
External IDs	OMIM: 106150 MGI: 87963 HomoloGene: 14 GeneCards: AGT Gene
Gene ontology
Molecular function	• serine-type endopeptidase inhibitor activity; • hormone activity; • protein binding; • growth factor activity; • superoxide-generating NADPH oxidase activator activity; • sodium channel regulator activity; • type 1 angiotensin receptor binding; • type 2 angiotensin receptor binding;
Cellular component	• extracellular region; • extracellular space; • cytoplasm; • extracellular exosome; • blood microparticle;
Biological process	• ovarian follicle rupture; • regulation of cell growth; • blood vessel development; • branching involved in ureteric bud morphogenesis; • positive regulation of cytokine production; • kidney development; • blood vessel remodeling; • angiotensin mediated vasoconstriction involved in regulation of systemic arterial blood pressure; • renal response to blood flow involved in circulatory renin-angiotensin regulation of systemic arterial blood pressure; • angiotensin maturation; • regulation of blood volume by renin-angiotensin; • renin-angiotensin regulation of aldosterone production; • regulation of renal output by angiotensin; • regulation of heart rate; • regulation of blood vessel size by renin-angiotensin; • renal system process; • angiotensin-mediated drinking behavior; • positive regulation of extracellular matrix constituent secretion; • cellular sodium ion homeostasis; • cell-matrix adhesion; • G-protein coupled receptor signaling pathway; • G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger; • phospholipase C-activating G-protein coupled receptor signaling pathway; • activation of phospholipase C activity; • activation of NF-kappaB-inducing kinase activity; • nitric oxide mediated signal transduction; • cell-cell signaling; • female pregnancy; • aging; • excretion; • establishment of blood-nerve barrier; • regulation of blood pressure; • negative regulation of cell proliferation; • response to cold; • response to salt stress; • positive regulation of activation of JAK2 kinase activity; • positive regulation of endothelial cell migration; • positive regulation of cardiac muscle hypertrophy; • positive regulation of macrophage derived foam cell differentiation; • positive regulation of cholesterol esterification; • negative regulation of endopeptidase activity; • regulation of norepinephrine secretion; • positive regulation of phosphatidylinositol 3-kinase signaling; • artery smooth muscle contraction; • response to muscle activity involved in regulation of muscle adaptation; • negative regulation of angiogenesis; • regulation of vasoconstriction; • extracellular matrix organization; • negative regulation of cell growth; • peristalsis; • positive regulation of cellular protein metabolic process; • positive regulation of superoxide anion generation; • positive regulation of peptidyl-serine phosphorylation; • positive regulation of NAD(P)H oxidase activity; • negative regulation of tissue remodeling; • low-density lipoprotein particle remodeling; • catenin import into nucleus; • regulation of renal sodium excretion; • positive regulation of renal sodium excretion; • positive regulation of multicellular organism growth; • regulation of cell proliferation; • vasodilation; • positive regulation of MAPK cascade; • negative regulation of neuron apoptotic process; • cellular lipid metabolic process; • cellular protein metabolic process; • small molecule metabolic process; • positive regulation of nitric oxide biosynthetic process; • positive regulation of fatty acid biosynthetic process; • positive regulation of epidermal growth factor receptor signaling pathway; • positive regulation of transcription, DNA-templated; • positive regulation of vasodilation; • positive regulation of organ growth; • astrocyte activation; • fibroblast proliferation; • positive regulation of fibroblast proliferation; • regulation of long-term neuronal synaptic plasticity; • smooth muscle cell proliferation; • cytokine secretion; • positive regulation of inflammatory response; • positive regulation of peptidyl-tyrosine phosphorylation; • positive regulation of NF-kappaB transcription factor activity; • smooth muscle cell differentiation; • negative regulation of neurotrophin TRK receptor signaling pathway; • stress-activated MAPK cascade; • regulation of calcium ion transport; • regulation of transmission of nerve impulse; • cell growth involved in cardiac muscle cell development; • positive regulation of protein tyrosine kinase activity; • ERK1 and ERK2 cascade; • uterine smooth muscle contraction; • cellular response to mechanical stimulus; • positive regulation of branching involved in ureteric bud morphogenesis; • positive regulation of protein kinase C activity; • regulation of extracellular matrix assembly; • positive regulation of membrane hyperpolarization; • positive regulation of gap junction assembly; • regulation of cardiac conduction; • positive regulation of reactive oxygen species metabolic process; • negative regulation of sodium ion transmembrane transporter activity; • positive regulation of extrinsic apoptotic signaling pathway;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

英: angiotensin III
関: アンジオテンシンIII

「II」

　　[★]

「I」

　　[★]

「angiotensin」

　　[★] アンジオテンシン

[pmid11751697-1] Basso N, Terragno NA (Dec 2001). "History about the discovery of the renin-angiotensin system". Hypertension 38 (6): 1246–9. doi:10.1161/hy1201.101214. PMID 11751697.

[2] "JAMA Article Jan 2012".

[isbn0-07-146633-9-3] Williams GH, Dluhy RG (2008). "Chapter 336: Disorders of the Adrenal Cortex". In Loscalzo J, Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL. Harrison's principles of internal medicine. McGraw-Hill Medical. ISBN 0-07-146633-9.

[4] Le, Tao (2012). First Aid for the Basic Sciences. Organ Systems. McGraw-Hill. p. 625.

[adipose_review-5] Yvan-Charvet L, Quignard-Boulangé A (Jan 2011). "Role of adipose tissue renin-angiotensin system in metabolic and inflammatory diseases associated with obesity". Kidney International 79 (2): 162–8. doi:10.1038/ki.2010.391. PMID 20944545.

[6] Kanaide, Hideo; Ichiki, Toshihiro; Nishimura, Junji; Hirano, Katsuya (2003-11-28). "Cellular Mechanism of Vasoconstriction Induced by Angiotensin II It Remains To Be Determined". Circulation Research 93 (11): 1015–1017. doi:10.1161/01.RES.0000105920.33926.60. ISSN 0009-7330. PMID 14645130.

[skurk-7] Skurk T, Lee YM, Hauner H (May 2001). "Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture". Hypertension 37 (5): 1336–40. doi:10.1161/01.HYP.37.5.1336. PMID 11358950.

[Gesualdo-8] Gesualdo L, Ranieri E, Monno R, Rossiello MR, Colucci M, Semeraro N, Grandaliano G, Schena FP, Ursi M, Cerullo G (Aug 1999). "Angiotensin IV stimulates plasminogen activator inhibitor-1 expression in proximal tubular epithelial cells". Kidney International 56 (2): 461–70. doi:10.1046/j.1523-1755.1999.00578.x. PMID 10432384.

[isbn1-4160-2328-3-9] Boulpaep EL, Boron WF (2005). Medical Physiology: a Cellular and Molecular Approach. St. Louis, Mo: Elsevier Saunders. p. 771. ISBN 1-4160-2328-3.

匿名

検索

案内

案内

angiotensin III