View source for Angiotensin

{{Short description|Group of peptide hormones in mammals}}
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{{More citations needed|date=March 2020}}
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'''Angiotensin''' is a [[peptide hormone]] that causes [[vasoconstriction]] and an increase in [[blood pressure]]. It is part of the [[renin–angiotensin system]], which regulates blood pressure. Angiotensin also stimulates the release of [[aldosterone]] from the [[adrenal cortex]] to promote sodium retention by the kidneys.

An [[oligopeptide]], angiotensin is a [[hormone]] and a [[dipsogen]]. It is derived from the precursor molecule angiotensinogen, a serum globulin produced in the [[liver]]. Angiotensin was isolated in the late 1930s (first named "angiotonin" or "hypertensin", later renamed "angiotensin" as a consensus by the 2 groups that independently discovered it<ref>See the first footnote:{{cite journal |last1=Hoobler |first1=Sibley |journal=Circulation |volume=17 |issue=4 |pages=825-832 |url=https://doi.org/10.1161/01.CIR.17.4.825 |title=An Interpretive Review of the Conference Proceedings |date=April 1958 |accessdate=2024-10-18}}</ref>) and subsequently characterized and synthesized by groups at the [[Cleveland Clinic]] and [[Ciba Specialty Chemicals|Ciba]] laboratories.<ref name="pmid11751697">{{cite journal | vauthors = Basso N, Terragno NA | title = History about the discovery of the renin-angiotensin system | journal = Hypertension | volume = 38 | issue = 6 | pages = 1246–9 | date = December 2001 | pmid = 11751697 | doi = 10.1161/hy1201.101214 | doi-access = free }}</ref>

== Precursor and types ==
{{Related|[[Angiotensin (1-7)]]}}

=== Angiotensinogen ===
[[File:Angiotensinogen.jpg|thumb|Crystal structure of reactive center loop cleaved angiotensinogen via x-ray diffraction]]
Angiotensinogen is an [[Alpha globulin|α-2-globulin]] synthesized in the liver<ref>{{cite web|title=Angiotensin {{!}} Hormone Health Network|url=https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/angiotensin|access-date=2019-12-02|website=www.hormone.org}}</ref> and is a precursor for angiotensin, but has also been indicated as having many other roles not related to angiotensin peptides.<ref name=":02">{{cite journal | vauthors = Lu H, Cassis LA, Kooi CW, Daugherty A | title = Structure and functions of angiotensinogen | journal = Hypertension Research | volume = 39 | issue = 7 | pages = 492–500 | date = July 2016 | pmid = 26888118 | pmc = 4935807 | doi = 10.1038/hr.2016.17 }}</ref> It is a member of the [[serpin]] family of proteins, leading to another name: Serpin A8,<ref>{{cite web|title=AGT - Angiotensinogen precursor - Homo sapiens (Human) - AGT gene & protein|url=https://www.uniprot.org/uniprot/P01019|access-date=2019-12-02|website=www.uniprot.org}}</ref> although it is not known to inhibit other enzymes like most serpins. In addition, a generalized crystal structure can be estimated by examining other proteins of the serpin family, but angiotensinogen has an elongated [[N-terminus]] compared to other serpin family proteins.<ref name=":12">{{cite journal | vauthors = Streatfeild-James RM, Williamson D, Pike RN, Tewksbury D, Carrell RW, Coughlin PB | title = Angiotensinogen cleavage by renin: importance of a structurally constrained N-terminus | journal = FEBS Letters | volume = 436 | issue = 2 | pages = 267–270 | date = October 1998 | pmid = 9781693 | doi = 10.1016/S0014-5793(98)01145-4 | s2cid = 29751589 | doi-access = free | bibcode = 1998FEBSL.436..267S }}</ref> Obtaining actual crystals for X-ray diffractometric analysis is difficult in part due to the variability of glycosylation that angiotensinogen exhibits. The non-glycosylated and fully glycosylated states of angiotensinogen also vary in molecular weight, the former weighing 53 kDa and the latter weighing 75 kDa, with a plethora of partially glycosylated states weighing in between these two values.<ref name=":02" />

Angiotensinogen is also known as [[renin]] substrate. It is cleaved at the N-terminus by renin to result in angiotensin I, which will later be modified to become angiotensin II.<ref name=":02" /><ref name=":12" /> This peptide is 485 amino acids long, and 10 N-terminus amino acids are cleaved when renin acts on it.<ref name=":02" /> The first 12 amino acids are the most important for activity.

:Amino acid sequence: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-...

Plasma angiotensinogen levels are increased by plasma [[corticosteroid]], [[estrogen]], [[thyroid]] [[hormone]], and angiotensin II levels. In mice with a full body deficit of angiotensinogen, the effects observed were low newborn survival rate, stunted body weight gain, stunted growth, and abnormal renal development.<ref name=":02" />

=== Angiotensin I ===

:Amino acid sequence: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu | Val-Ile-...

[[Image:Renin-angiotensin-aldosterone system.svg|thumb|[[Renin–angiotensin–aldosterone system]]|480x480px]]

Angiotensin I ([[CAS registry number|CAS]]# 11128-99-7), officially called '''proangiotensin''', 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 [[Peptide#Notes on terminology|decapeptide]] (ten amino acid) (des-Asp) angiotensin I. Renin is produced in the [[kidney]]s in response to renal sympathetic activity, decreased intrarenal blood pressure (<90mmHg systolic blood pressure<ref>{{cite journal | vauthors = Preston RA, Materson BJ, Reda DJ, Williams DW, Hamburger RJ, Cushman WC, Anderson RJ | title = Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents | journal = JAMA | volume = 280 | issue = 13 | pages = 1168–72 | date = October 1998 | pmid = 9777817 | doi = 10.1001/jama.280.13.1168 | doi-access = free }}</ref> ) at the [[juxtaglomerular cell]]s, dehydration or decreased delivery of Na+ and Cl- to the [[macula densa]].<ref name="isbn0-07-146633-9">{{cite book |veditors=Loscalzo J, Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL | title = Harrison's principles of internal medicine | publisher = McGraw-Hill Medical | year = 2008 | isbn = 978-0-07-146633-2 |vauthors=Williams GH, Dluhy RG | chapter = Chapter 336: Disorders of the Adrenal Cortex }}</ref>  If a reduced NaCl concentration<ref>{{cite journal | vauthors = Skott O, Briggs JP | year = 1987 | title = Direct demonstration of macula densa-mediated renin secretion | journal = Science | volume = 237 | issue = 4822| pages = 1618–1620 | doi=10.1126/science.3306925| pmid = 3306925 | bibcode = 1987Sci...237.1618S }}</ref> in the distal tubule is sensed by the macula densa, renin release by juxtaglomerular cells is increased. This sensing mechanism for macula densa-mediated renin secretion appears to have a specific dependency on chloride ions rather than sodium ions. Studies using isolated preparations of [[thick ascending limb]] with [[Glomerulus (kidney)|glomerulus]] attached in low NaCl perfusate were unable to inhibit renin secretion when various sodium salts were added but could inhibit renin secretion with the addition of [[chloride]] salts.<ref name="pmid31796">{{cite journal | vauthors = Kirchner KA, Kotchen TA, Galla JH, Luke RG | title = Importance of chloride for acute inhibition of renin by sodium chloride | journal = The American Journal of Physiology | volume = 235 | issue = 5 | pages = F444–50 | date = November 1978 | pmid = 31796 | doi = 10.1152/ajprenal.1978.235.5.F444 }}</ref> This, and similar findings obtained in vivo,<ref name="pmid16303857">{{cite journal | vauthors = Kim SM, Mizel D, Huang YG, Briggs JP, Schnermann J | title = Adenosine as a mediator of macula densa-dependent inhibition of renin secretion | journal = American Journal of Physiology. Renal Physiology | volume = 290 | issue = 5 | pages = F1016–23 | date = May 2006 | pmid = 16303857 | doi = 10.1152/ajprenal.00367.2005 | s2cid = 270730 }}</ref> has led some to believe that perhaps "the initiating signal for MD control of renin secretion is a change in the rate of NaCl uptake predominantly via a luminal [[Na-K-Cl cotransporter|Na,K,2Cl co-transporter]] whose physiological activity is determined by a change in luminal Cl concentration."<ref name="Schnermann_2013">{{cite book | vauthors = Schnermann JB, Castrop H | title = Seldin and Giebisch's the Kidney | chapter = Function of the Juxtaglomerular Apparatus | pages = 757–801 | veditors = Alpern RJ, Moe OW, Caplan M | publisher = Academic Press | edition = Fifth | year = 2013 | isbn = 978-0-12-381462-3 | doi = 10.1016/B978-0-12-381462-3.00023-9 }}</ref>

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

=== Angiotensin II ===
{{see also|Angiotensin II (medication)}}

:Amino acid sequence: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe

==== Production ====
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]], kidney epithelial cells, and the brain).{{Citation needed|date=June 2025}}

==== Degradation ====
Angiotensin II is degraded to angiotensin III by angiotensinases located in red blood cells and the vascular beds of most tissues. Angiotensin II has a half-life in circulation of around 30 seconds,<ref>{{cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK499912/ |title=StatPearls |vauthors=Patel P, Sanghavi D, Morris DL, Kahwaji CI |date=2023 |publisher=StatPearls Publishing |location=Treasure Island (FL) |chapter=Angiotensin II |pmid=29763087}}</ref> whereas, in tissue, it may be as long as 15–30 minutes. Other cleavage products of ACE, seven or nine amino acids long, are also known; they have differential affinity for [[angiotensin receptors]], although their exact role is still unclear.

==== Physiological effects ====
Angiotensin II exhibits [[endocrine system|endocrine]], [[autocrine signalling|autocrine]]/[[paracrine signalling|paracrine]], and [[intracrine]] functions.

It promotes [[aldosterone]] release from the [[adrenal cortex]], as well as [[vasopressin|arginine vasopressin]] release from the [[posterior pituitary]].{{Citation needed|date=June 2025}}

It acts directly upon the [[proximal tubule]]s of the kidney to regulate water and Na+ reabsorption, promoting reabsorption at very low concentrations while increasingly inhibiting reabsorption with increasing concentrations.<ref>{{Cite book |last=Greger |first=Rainer |title=Comprehensive Human Physiology: From Cellular Mechanisms to Integration |last2=Windhorst |first2=Uwe |date= |publisher=Springer |others= |year=1996 |isbn=978-3-642-60946-6 |location=Berlin, Heidelberg |publication-date= |pages=1518}}</ref> In the proximal tubule, it promotes Na<sup>+</sup> reabsorption and H<sup>+</sup> excretion (which is coupled to bicarbonate reabsorption) by the [[Na+/H+ exchanger|Na<sup>+</sup>/H<sup>+</sup> exchanger]].<ref name=":0" />

It causes venous and arterial{{Citation needed|date=June 2025}} vasoconstriction by a [[Gq alpha subunit]]-coupled receptor upon vascular smooth muscle cells (with downstream IP3-dependent mechanism causing a rise in intracellular Ca<sup>2+</sup> to effect smooth muscle [[Excitation contraction coupling|excitation-contraction coupling]]), thus acting to increase blood pressure.<ref name=":0" />

==== Pharmacological significance ====
ACE is a pharmaceutical target of [[ACE inhibitor]] drugs, which decrease the rate of conversion of angiotensin I to angiotensin II,<ref name=":0">{{cite book| vauthors  = Le T |title=First Aid for the Basic Sciences. Organ Systems|year=2012|publisher=McGraw-Hill|page=625}}</ref> and of [[angiotensin II receptor antagonist]]s which block [[Angiotensin receptor|angiotensin II AT<sub>1</sub> receptors]].

Angiotensin II results in increased [[inotrope|inotropy]], [[chronotropic|chronotropy]], [[catecholamine]] and sensitivity, aldosterone levels, vasopressin levels, and cardiac remodeling and vasoconstriction through AT<sub>1</sub> receptors on peripheral vessels (conversely, AT<sub>2</sub> receptors impair cardiac remodeling). This is why ACE inhibitors and ARBs help to prevent remodeling that occurs secondary to angiotensin II and are beneficial in [[congestive heart failure]].<ref name="Schnermann_2013" />{{Further explanation needed|date=June 2025}}

=== Angiotensin III ===

:Amino acid sequence: Asp | Arg-Val-Tyr-Ile-His-Pro-Phe

Angiotensin III, along with angiotensin II, is considered an active peptide derived from angiotensinogen.<ref>{{cite journal | vauthors = Wright JW, Mizutani S, Harding JW | title = Focus on Brain Angiotensin III and Aminopeptidase A in the Control of Hypertension | journal = International Journal of Hypertension | volume = 2012 | pages = 124758 | date = 2012 | pmid = 22792446 | doi = 10.1155/2012/124758 | pmc = 3389720 | doi-access = free }}</ref>

Angiotensin III has 40% of the [[Vasoconstrictor|pressor]] activity of angiotensin II, but 100% of the aldosterone-producing activity. Increases [[mean arterial pressure]]. It is a peptide that is formed by removing an amino acid from angiotensin II by [[glutamyl aminopeptidase]] A, which cleaves the N-terminal Asp residue.<ref>{{cite web|title=Angiotensin III|url=https://pubchem.ncbi.nlm.nih.gov/compound/angiotensin_iii|access-date=9 May 2019|website=PubChem|publisher=NIH}}</ref>

Activation of the AT2 receptor by angiotensin III triggers [[natriuresis]], while AT2 activation via angiotensin II does not. This natriuretic response via angiotensin III occurs when the AT1 receptor is blocked.<ref>{{cite journal | vauthors = Padia SH, Howell NL, Siragy HM, Carey RM | title = Renal angiotensin type 2 receptors mediate natriuresis via angiotensin III in the angiotensin II type 1 receptor-blocked rat | journal = Hypertension | volume = 47 | issue = 3 | pages = 537–544 | date = March 2006 | pmid = 16380540 | doi = 10.1161/01.HYP.0000196950.48596.21 | s2cid = 37807540 | doi-access =  }}</ref>

=== Angiotensin IV ===

:Amino acid sequence: Arg | Val-Tyr-Ile-His-Pro-Phe

Angiotensin IV is a hexapeptide that, like angiotensin III, has some lesser activity. Angiotensin IV has a wide range of activities in the central nervous system.<ref>{{cite journal | vauthors = Chai SY, Fernando R, Peck G, Ye SY, Mendelsohn FA, Jenkins TA, Albiston AL | title = The angiotensin IV/AT4 receptor | journal = Cellular and Molecular Life Sciences | volume = 61 | issue = 21 | pages = 2728–2737 | date = November 2004 | pmid = 15549174 | doi = 10.1007/s00018-004-4246-1 | s2cid = 22816307 | pmc = 11924499 }}</ref><ref name="pmid190909882">{{cite journal | vauthors = Gard PR | title = Cognitive-enhancing effects of angiotensin IV | journal = BMC Neuroscience | volume = 9 | issue = Suppl 2 | pages = S15 | date = December 2008 | pmid = 19090988 | pmc = 2604899 | doi = 10.1186/1471-2202-9-S2-S15 | doi-access = free }}</ref>

The exact identity of AT4 receptors has not been established. There is evidence that the AT4 receptor is [[Leucyl/cystinyl aminopeptidase|insulin-regulated aminopeptidase]] (IRAP).<ref>{{cite journal|vauthors=Albiston AL, McDowall SG, Matsacos D, Sim P, Clune E, Mustafa T, Lee J, Mendelsohn FA, Simpson RJ, Connolly LM, Chai SY|date=December 2001|title=Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase|journal=The Journal of Biological Chemistry|volume=276|issue=52|pages=48623–6|doi=10.1074/jbc.C100512200|pmid=11707427|doi-access=free}}</ref> There is also evidence that angiotensin IV interacts with the HGF system through the c-Met receptor.<ref>{{cite journal|vauthors=Wright JW, Harding JW|date=2015-01-01|title=The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease|journal=Journal of Alzheimer's Disease|volume=45|issue=4|pages=985–1000|doi=10.3233/JAD-142814|pmid=25649658}}</ref><ref name="Wright_20152">{{cite journal|vauthors=Wright JW, Kawas LH, Harding JW|date=February 2015|title=The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases|journal=Progress in Neurobiology|volume=125|pages=26–46|doi=10.1016/j.pneurobio.2014.11.004|pmid=25455861|s2cid=41360989}}</ref>

Synthetic [[small molecule]] analogues of angiotensin IV with the ability to penetrate through [[blood brain barrier]] have been developed.<ref name="Wright_20152" />

The AT4 site may be involved in memory acquisition and recall, as well as blood flow regulation.<ref name="pmid77683212">{{cite journal | vauthors = Wright JW, Krebs LT, Stobb JW, Harding JW | title = The angiotensin IV system: functional implications | journal = Frontiers in Neuroendocrinology | volume = 16 | issue = 1 | pages = 23–52 | date = January 1995 | pmid = 7768321 | doi = 10.1006/frne.1995.1002 | s2cid = 20552386 }}</ref> Angiotensin IV and its analogs may also benefit spatial memory tasks such as object recognition and avoidance (conditioned and passive avoidance).<ref name=":03">{{cite journal | vauthors = Ho JK, Nation DA | title = Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies | journal = Neuroscience and Biobehavioral Reviews | volume = 92 | pages = 209–225 | date = September 2018 | pmid = 29733881 | doi = 10.1016/j.neubiorev.2018.05.005 | pmc = 8916541 | s2cid = 13686581 }}</ref> Studies have also shown that the usual biological effects of angiotensin IV on the body are not affected by common AT2 receptor antagonists such as the hypertension medication [[Losartan]].<ref name=":03" />

== Effects ==<!--Renin–angiotensin_system has a link to here-->
:''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."<ref name="adipose review">{{cite journal | vauthors = Yvan-Charvet L, Quignard-Boulangé A | title = Role of adipose tissue renin-angiotensin system in metabolic and inflammatory diseases associated with obesity | journal = Kidney International | volume = 79 | issue = 2 | pages = 162–8 | date = January 2011 | pmid = 20944545 | doi = 10.1038/ki.2010.391 | doi-access = free }}</ref>

=== Cardiovascular ===

Angiotensins are potent direct [[vasoconstrictor]]s, constricting arteries and increasing blood pressure. This effect is achieved through activation of the [[Angiotensin II receptor type 1|GPCR AT<sub>1</sub>]], which signals through a [[Gq alpha subunit|Gq protein]] to activate phospholipase C, and subsequently increase intracellular calcium.<ref>{{cite journal | vauthors = Kanaide H, Ichiki T, Nishimura J, Hirano K | title = Cellular mechanism of vasoconstriction induced by angiotensin II: it remains to be determined | journal = Circulation Research | volume = 93 | issue = 11 | pages = 1015–7 | date = November 2003 | pmid = 14645130 | doi = 10.1161/01.RES.0000105920.33926.60 | doi-access = free }}</ref>

Angiotensin II has prothrombotic potential through adhesion and aggregation of [[platelets]] and stimulation of [[plasminogen activator inhibitor 1|PAI-1]] and [[plasminogen activator inhibitor 2|PAI-2]].<ref name="skurk">{{cite journal | vauthors = Skurk T, Lee YM, Hauner H | title = Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture | journal = Hypertension | volume = 37 | issue = 5 | pages = 1336–40 | date = May 2001 | pmid = 11358950 | doi = 10.1161/01.HYP.37.5.1336 | doi-access = free }}</ref><ref name="Gesualdo">{{cite journal | vauthors = Gesualdo L, Ranieri E, Monno R, Rossiello MR, Colucci M, Semeraro N, Grandaliano G, Schena FP, Ursi M, Cerullo G | title = Angiotensin IV stimulates plasminogen activator inhibitor-1 expression in proximal tubular epithelial cells | journal = Kidney International | volume = 56 | issue = 2 | pages = 461–70 | date = August 1999 | pmid = 10432384 | doi = 10.1046/j.1523-1755.1999.00578.x | doi-access = free }}</ref>

=== Neural ===

Angiotensin II increases [[thirst]] sensation ([[dipsogen]]) through the [[area postrema]] and [[subfornical organ]] of the brain,<ref name="johnson">{{cite journal | vauthors = Johnson AK, Gross PM | title = Sensory circumventricular organs and brain homeostatic pathways | journal = FASEB Journal | volume = 7 | issue = 8 | pages = 678–86 | date = May 1993 | pmid = 8500693 | doi=10.1096/fasebj.7.8.8500693| doi-access = free | s2cid = 13339562 }}</ref><ref>{{cite journal | vauthors = Shaver SW, Kadekaro M, Gross PM | title = High metabolic activity in the dorsal vagal complex of Brattleboro rats | journal = Brain Research | volume = 505 | issue = 2 | pages = 316–20 | date = December 1989 | pmid = 2598049 | doi=10.1016/0006-8993(89)91459-5| s2cid = 32921413 }}</ref><ref name="gross2">{{cite journal | vauthors = Gross PM, Wainman DS, Shaver SW, Wall KM, Ferguson AV | title = Metabolic activation of efferent pathways from the rat area postrema | journal = The American Journal of Physiology | volume = 258 | issue = 3 Pt 2 | pages = R788-97 | date = March 1990 | pmid = 2316724 | doi = 10.1152/ajpregu.1990.258.3.R788 }}</ref> decreases the response of the [[baroreceptor reflex]], increases the desire for [[table salt|salt]], increases secretion of [[vasopressin|ADH]] from the [[posterior pituitary]], and increases secretion of [[corticotropin|ACTH]] from the [[anterior pituitary]].<ref name=johnson/> Some evidence suggests that it acts on the [[Vascular organ of lamina terminalis|organum vasculosum of the lamina terminalis (OVLT)]] as well.<ref>{{cite book | vauthors = Barrett KE, Barman SM, Brooks HL, Yuan JX, Ganong WF |url=https://www.worldcat.org/oclc/1076268769 |title=Ganong's review of medical physiology |date=2019 |isbn=978-1260122404 |edition=26th |location = New York | publisher =  McGraw-Hill Education |pages=304 |oclc=1076268769}}</ref>

=== 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<sup>+</sup> [[absorption (chemistry)|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.

{|class="wikitable"
|+ Direct Renal effects of angiotensin II (not including [[aldosterone]] release)
|-
!Target
!Action
!Mechanism<ref name="isbn1-4160-2328-3">{{cite book |vauthors=Boulpaep EL, Boron WF | title = Medical Physiology: a Cellular and Molecular Approach | publisher = Elsevier Saunders | location = St. Louis, Mo | year = 2005 | pages = 771 | isbn = 978-1-4160-2328-9 }}</ref>
|-
![[renal artery]] & <br> [[afferent arterioles]]
| [[vasoconstriction]] (weaker) || [[Voltage-dependent calcium channel|VDCC]]s → [[calcium|Ca<sup>2+</sup>]] influx
|-
! [[efferent arteriole]]
| [[vasoconstriction]] (stronger) || (probably) activate [[Angiotensin receptor#AT1|Angiotensin receptor 1]] → Activation of [[gq alpha subunit|G<sub>q</sub>]] → ↑[[phospholipase C|PLC]] activity → ↑[[Inositol triphosphate|IP<sub>3</sub>]] and [[diacylglycerol|DAG]] → activation of [[Inositol triphosphate receptor|IP<sub>3</sub> receptor]] in [[sarcoplasmic reticulum|SR]] → ↑intracellular Ca<sup>2+</sup>
|-
![[mesangial cell]]s
| contraction → ↓filtration area ||
* activation of [[gq alpha subunit|G<sub>q</sub>]] → ↑[[phospholipase C|PLC]] activity → ↑[[Inositol triphosphate|IP<sub>3</sub>]] and [[diacylglycerol|DAG]] → activation of [[Inositol triphosphate receptor|IP<sub>3</sub> receptor]] in [[sarcoplasmic reticulum|SR]] → ↑intracellular Ca<sup>2+</sup>
* [[Voltage-dependent calcium channel|VDCC]]s → [[calcium|Ca<sup>2+</sup>]] influx
|-
![[proximal tubule]]
| increased Na<sup>+</sup> 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]]
|-
! [[renal medulla|medullary]] blood flow
| reduction ||
|-
|}

== See also ==
{{col div|colwidth=30em}}
* [[ACE inhibitor]]
* [[Angiotensin receptor]]
* [[Angiotensin II receptor antagonist]]
* [[Captopril]]
* [[Perindopril]]
* [[Renin inhibitor]]
{{colend}}

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T | title = International union of pharmacology. XXIII. The angiotensin II receptors | journal = Pharmacological Reviews | volume = 52 | issue = 3 | pages = 415–72 | date = September 2000 | pmid = 10977869 }}
* ''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.
* ''Clinical Physiology of Acid-Base and Electrolyte Disorders'', 5th ed., Burton David Rose & Theodore W. Post McGraw-Hill, 2001
* {{cite journal | vauthors = Lees KR, MacFadyen RJ, Doig JK, Reid JL | title = Role of angiotensin in the extravascular system | journal = Journal of Human Hypertension | volume = 7 | issue = Suppl 2 | pages = S7-12 | date = August 1993 | pmid = 8230088 }}
* {{cite journal | vauthors = Weir MR, Dzau VJ | title = The renin-angiotensin-aldosterone system: a specific target for hypertension management | journal = American Journal of Hypertension | volume = 12 | issue = 12 Pt 3 | pages = 205S–213S | date = December 1999 | pmid = 10619573 | doi = 10.1016/S0895-7061(99)00103-X | doi-access = free }}
* {{cite journal | vauthors = Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG | title = Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 281 | issue = 6 | pages = H2337-65 | date = December 2001 | pmid = 11709400 | doi = 10.1152/ajpheart.2001.281.6.H2337 | s2cid = 41296327 }}
* {{cite journal | vauthors = Varagic J, Frohlich ED | title = Local cardiac renin-angiotensin system: hypertension and cardiac failure | journal = Journal of Molecular and Cellular Cardiology | volume = 34 | issue = 11 | pages = 1435–42 | date = November 2002 | pmid = 12431442 | doi = 10.1006/jmcc.2002.2075 }}
* {{cite journal | vauthors = Wolf G | title = Role of reactive oxygen species in angiotensin II-mediated renal growth, differentiation, and apoptosis | journal = Antioxidants & Redox Signaling | volume = 7 | issue = 9–10 | pages = 1337–45 | year = 2006 | pmid = 16115039 | doi = 10.1089/ars.2005.7.1337 }}
* {{cite journal | vauthors = Cazaubon S, Deshayes F, Couraud PO, Nahmias C | title = [Endothelin-1, angiotensin II and cancer] | journal = Médecine/Sciences | volume = 22 | issue = 4 | pages = 416–22 | date = April 2006 | pmid = 16597412 | doi = 10.1051/medsci/2006224416 | doi-access = free }}
* {{cite journal | vauthors = Ariza AC, Bobadilla NA, Halhali A | title = [Endothelin 1 and angiotensin II in preeeclampsia] | journal = Revista de Investigacion Clinica| volume = 59 | issue = 1 | pages = 48–56 | year = 2007 | pmid = 17569300 }}
{{refend}}

== External links ==
{{commons category|Angiotensin}}
* The [[MEROPS]] online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=I04.953 I04.953] {{Webarchive|url=https://web.archive.org/web/20191016155606/http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=I04.953 |date=2019-10-16 }}
* {{MeshName|Angiotensins}}
* {{UCSC gene info|AGT}}
* {{PDBe-KB2|P01019|Angiotensin}}

{{Cardiovascular physiology}}
{{Neuropeptides}}
{{Autacoids}}
{{Angiotensin receptor modulators}}
{{Authority control}}

[[Category:Peptide hormones]]
[[Category:Angiology]]
[[Category:Endocrinology]]
[[Category:Hypertension]]
[[Category:Hexapeptides]]
[[Category:Decapeptides]]
[[Category:Octapeptides]]