Renin-angiotensin system
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224971005
2008-07-11T06:48:43Z
Mjms1962
6963683
/* Effects */
The '''renin-angiotensin system''' (RAS) or the '''renin-angiotensin-aldosterone system''' (RAAS) is a hormone system that regulates [[blood pressure]] and water ([[extracellular fluid|fluid]]) balance.
When blood pressure is low, the kidneys secrete [[renin]]. Renin stimulates the production of [[angiotensin]]. Angiotensin causes blood vessels to constrict resulting in increased blood pressure. Angiotensin also stimulates the secretion of the hormone [[aldosterone]] from the [[adrenal cortex]]. Aldosterone causes the tubules of the kidneys to retain sodium and water. This increases the volume of fluid in the body, which also increases blood pressure.
If the renin-angiotensin-aldosterone system is too active, blood pressure will be too high. There are many drugs which interrupt different steps in this system to lower blood pressure. These drugs are one of the main ways to control high blood pressure ([[hypertension]]), [[heart failure]], [[kidney failure]], and harmful effects of [[diabetes]].<ref>{{cite web |url=http://www.merck.com/mmhe/sec03/ch022/ch022a.html |title=High Blood Pressure: Heart and Blood Vessel Disorders |format= |work=Merck Manual Home Edition |accessdate=}}</ref><ref>{{cite journal
| last = Solomon
| first = Scott D
| coauthors = Anavekar, Nagesh
| title = A Brief Overview of Inhibition of the Renin-Angiotensin System: Emphasis on Blockade of the Angiotensin II Type-1 Receptor
| journal = Medscape Cardiology
| volume = 9
| issue = 2
| publisher =
| location =
| year = 2005
| url =http://www.medscape.com/viewarticle/503909
| doi =
| id =
| accessdate = }}
</ref>
==Activation==
The system can be activated when there is a loss of [[blood]] volume or a drop in [[blood pressure]] (such as in [[hemorrhage]]).
# If the perfusion of the [[juxtaglomerular apparatus]] in the [[kidney]]s decreases, then the juxtaglomerular cells release the [[enzyme|enzyme]] [[renin]].
# Renin cleaves an inactive [[peptide]] called ''[[angiotensinogen]]'', converting it into ''[[angiotensin|angiotensin I]]''.
# Angiotensin I is then converted to ''[[angiotensin|angiotensin II]]'' by [[angiotensin-converting enzyme]] (ACE)<ref>{{cite journal |author=Paul M, Poyan Mehr A, Kreutz R |title=Physiology of local renin-angiotensin systems |journal=Physiol. Rev. |volume=86 |issue=3 |pages=747–803 |year=2006 |month=July |pmid=16816138 |doi=10.1152/physrev.00036.2005 |url=http://physrev.physiology.org/cgi/content/full/86/3/747}}</ref> which is found mainly in [[lung]] [[capillaries]].
# Angiotensin II is the major bioactive product of the renin-angiotensin system. Angiotensin II acts as an [[endocrine system | endocrine]], [[autocrine signalling | autocrine]]/[[paracrine signalling | paracrine]], and [[intracrine]] hormone.
# Patil Jaspal et. al. has shown local synthesis of Angiotensin II in neurons of sympathetic ganglia.<ref>{{cite journal |author=Patil J, Heiniger E, Schaffner T, Mühlemann O, Imboden H |title=Angiotensinergic neurons in sympathetic coeliac ganglia innervating rat and human mesenteric resistance blood vessels |journal=Regul. Pept. |volume=147 |issue=1-3 |pages=82–7 |year=2008 |month=April |pmid=18308407 |doi=10.1016/j.regpep.2008.01.006 |url=}}</ref>
==Effects==
:''Further reading: [[Angiotensin#Effects]] and [[Aldosterone#Function]]''
It is believe that Angiotensin I may have some minor activity, but angiotensin II is the major bio-active product. Angiotensin II has a variety of effects on the body:
*Throughout the body, it is a potent [[vasoconstrictor]] of [[arterioles]].
*In the [[kidney]]s, it constricts [[Glomerulus (kidney)|glomerular]] arterioles, having a greater effect on [[efferent arterioles]] than afferent. As with most other capillary beds in the body, the constriction of [[afferent arterioles]] increases the arteriolar resistance, raising [[systemic circulation|systemic]] [[arterial blood pressure]] and decreasing the blood flow. However, the kidneys must continue to filter enough blood despite this drop in blood flow, necessitating mechanisms to keep glomerular blood pressure up. To do this, Angiotensin II constricts efferent arterioles, which forces blood to build up in the glomerulus, increasing glomerular pressure. The [[glomerular filtration rate]] (GFR) is thus maintained, and blood filtration can continue despite lowered overall kidney blood flow.
*In the [[adrenal cortex]], it acts to cause the release of [[aldosterone]]. Aldosterone acts on the tubules (e.g the [[distal convoluted tubule]]s and the [[renal cortex|cortical]] [[collecting duct]]s) in the kidneys, causing them to reabsorb more [[sodium]] and water from the [[urine]]. [[Potassium]] is secreted into the tubules in exchange for the sodium, which is excreted. Aldosterone also acts on the [[central nervous system]] to increase an individual's appetite for salt, and to stimulate the sensation of [[thirst]].
*Release of Anti-Diuretic Hormone (ADH), also called [[vasopressin]] -- ADH is made in the hypothalamus and released from the posterior [[pituitary gland]]. As its name suggests, it also exhibits vaso-constrictive properties, but its main course of action is to stimulate reabsorption of water in the kidneys.
These effects directly act in concert to increase blood pressure.
==Clinical significance==
The renin-angiotensin system is often manipulated clinically to treat [[high blood pressure]].
* [[ACE inhibitor|Inhibitors of angiotensin-converting enzyme]] (ACE inhibitors) are often used to reduce the formation of the more potent angiotensin II. [[Captopril]] is an example of an ACE inhibitor.
* Alternatively, [[angiotensin II receptor antagonist|angiotensin receptor blockers]] (ARBs) can be used to prevent angiotensin II from acting on [[angiotensin receptor]]s.
* A new drug called [[Aliskiren]] released in 2007 acts by directly inhibiting renin receptors.
==Other uses of ACE==
Interestingly, ACE cleaves a number of other peptides, and in this capacity is an important regulator of the [[kinin-kallikrein system]].
== Fetal renin-angiotensin system ==
In the [[fetus]], the renin-angiotensin system is predominantly a sodium-losing system, as angiotensin II has little or no effect on aldosterone levels. Renin levels are high in the fetus, while angiotensin II levels are significantly lower — this is due to the limited pulmonary blood flow, preventing ACE (found predominantly in the pulmonary circulation) from having its maximum effect.
==References==
{{reflist}}
* {{cite journal |author=Banic A, Sigurdsson GH, Wheatley AM |title=Influence of age on the cardiovascular response during graded haemorrhage in anaesthetized rats |journal=Res Exp Med (Berl) |volume=193 |issue=5 |pages=315–21 |year=1993 |pmid=8278677 |doi= |url=}}
==External links==
* {{MeshName|Renin-Angiotensin+System}}
{{Cardiovascular physiology}}
{{renal physiology}}
[[Category:Cardiovascular system]]
[[Category:Endocrinology]]
[[da:Renin-angiotensin-aldosteron-systemet]]
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[[fr:Système rénine-angiotensine-aldostérone]]
[[it:Sistema renina-angiotensina]]
[[he:מערכת הרנין-אנגיוטנסין-אלדוסטרון]]
[[nl:Bloeddrukregulatie]]
[[ja:レニン-アンギオテンシン系]]
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[[pl:RAA]]
[[pt:Sistema renina-angiotensina]]
[[ru:Ренин-ангиотензиновая система]]
[[sk:Systém renín-angiotenzín-aldosterón]]
[[sv:Renin-angiotensinsystemet]]