View source for Renin–angiotensin system/ja

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[[File:Renin-angiotensin system in man shadow.svg|thumb|250px|RASの解剖図]]
'''レニン-アンジオテンシン系'''（'''RAS'''）、または'''レニン-アンジオテンシン-アルドステロン系'''（'''RAAS'''）は、[[blood pressure/ja|血圧]]、[[fluid balance/ja|体液バランス]]、[[electrolyte/ja|電解質]]バランス、および全身の[[vascular resistance/ja|血管抵抗]]を調節する[[endocrine system/ja|ホルモン系]]である。

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When [[Kidney#Blood supply|renal blood flow]] is reduced, [[juxtaglomerular cell]]s in the kidneys convert the precursor [[prorenin]] (already present in the blood) into [[renin]] and secrete it directly into the [[circulatory system|circulation]]. Plasma renin then carries out the conversion of [[angiotensinogen]], released by the [[liver]], to a decapeptide called [[angiotensin I]]. Angiotensin I is subsequently converted to [[angiotensin II]] (an octapeptide) by the [[angiotensin-converting enzyme]] (ACE) found on the surface of vascular endothelial cells, predominantly those of the [[lung]]s. Angiotensin II has a short life of about 1 to 2 minutes. Then, it is rapidly degraded into a heptapeptide called [[angiotensin III]] by angiotensinases which are present in [[red blood cell]]s and vascular beds in many tissues.
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Angiotensin III increases blood pressure and stimulates aldosterone secretion from the adrenal cortex; it has 100% adrenocortical stimulating activity and 40% vasopressor activity of angiotensin II.
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[[Angiotensin IV]] also has adrenocortical and vasopressor activities
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Angiotensin II is a potent [[vasoconstriction|vasoconstrictive]] peptide that causes blood vessels to narrow, resulting in increased blood pressure. Angiotensin II also stimulates the secretion of the hormone [[aldosterone]] from the [[adrenal cortex]]. Aldosterone causes the [[Distal convoluted tubule|renal tubules]] to increase the reabsorption of [[sodium in biology|sodium]] which in consequence causes the reabsorption of water into the blood, while at the same time causing the excretion of [[potassium]] (to maintain [[electrolyte]] balance). This increases the volume of [[extracellular fluid]] in the body, which also increases blood pressure.
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If the RAS is abnormally active, blood pressure will be too high. There are several types of drugs which includes [[ACE inhibitors]], [[angiotensin II receptor blocker]]s (ARBs), and [[renin inhibitors]] that interrupt different steps in this system to improve blood pressure. These drugs are one of the primary ways to control [[hypertension|high blood pressure]], [[heart failure]], [[kidney failure]], and harmful effects of [[diabetes]].
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==Activation==
{{Further|Autoregulation#Renal regulation}}
[[Image:Renin-angiotensin-aldosterone system.svg|thumb|center|700px|RAAS schematic]]
The system can be activated when there is a loss of [[blood volume]] or a drop in [[blood pressure]] (such as in [[hemorrhage]] or [[dehydration]]). This loss of pressure is interpreted by [[baroreceptor]]s in the [[carotid sinus]]. It can also be activated by a decrease in the filtrate [[sodium chloride]] (NaCl) concentration or a decreased filtrate flow rate that will stimulate the [[macula densa]] to signal the [[juxtaglomerular cell]]s to release renin.
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# If the perfusion of the [[juxtaglomerular apparatus]] in the kidney's [[macula densa]] decreases, then the juxtaglomerular cells (granular cells, modified pericytes in the glomerular capillary) release the [[enzyme]] [[renin]].
# Renin [[Proteolysis#Cleavage of precursor proteins|cleaves]] a [[Peptide#Notes on terminology|decapeptide]] from [[angiotensinogen]], a [[globular protein]]. The decapeptide is known as [[Angiotensin#Angiotensin I|angiotensin I]].
# Angiotensin I is then converted to an [[Peptide#Notes on terminology|octapeptide]], ''[[angiotensin|angiotensin II]]'' by [[angiotensin-converting enzyme]] (ACE), which is thought to be found mainly in endothelial cells of the [[capillary|capillaries]] throughout the body, within the lungs and the epithelial cells of the kidneys. One study in 1992 found ACE in all blood vessel endothelial cells.
# Angiotensin II is the major bioactive product of the renin–angiotensin system, binding to receptors on [[intraglomerular mesangial cells]], causing these cells to contract along with the blood vessels surrounding them; and to receptors on the zona glomerulosa cells, causing the release of [[aldosterone]] from the [[zona glomerulosa]] in the [[adrenal cortex]]. Angiotensin II acts as an [[endocrine system|endocrine]], [[autocrine signalling|autocrine]]/[[paracrine signalling|paracrine]], and [[intracrine]] hormone.
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==Cardiovascular effects==
{{Further|Angiotensin#Effects|Aldosterone#Biological function}}
[[File:RenalHormoneRegulation.png|thumb|350px |Renal hormone regulation schematic]]
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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, angiotensin II is a potent [[vasoconstrictor]] of [[arteriole]]s.
* In the kidneys, angiotensin II 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. Because the filtration fraction, which is the ratio of the glomerular filtration rate (GFR) to the renal plasma flow (RPF), has increased, there is less plasma fluid in the downstream peritubular capillaries. This in turn leads to a decreased [[hydrostatic pressure]] and increased [[oncotic pressure]] (due to unfiltered [[plasma proteins]]) in the peritubular capillaries. The effect of decreased hydrostatic pressure and increased oncotic pressure in the peritubular capillaries will facilitate increased reabsorption of tubular fluid.
* Angiotensin II decreases medullary blood flow through the [[Straight arterioles of kidney|vasa recta]]. This decreases the washout of NaCl and [[urea]] in the kidney [[Renal medulla|medullary space]]. Thus, higher concentrations of NaCl and urea in the medulla facilitate increased absorption of tubular fluid. Furthermore, increased reabsorption of fluid into the medulla will increase passive reabsorption of sodium along the thick ascending limb of the [[Loop of Henle]].
* Angiotensin II stimulates {{chem|Na|+}}/{{chem|H|+}} exchangers located on the apical membranes (faces the tubular lumen) of cells in the proximal tubule and thick ascending limb of the loop of Henle in addition to {{chem|Na|+}} channels in the collecting ducts. This will ultimately lead to increased sodium reabsorption.
* Angiotensin II stimulates the hypertrophy of renal tubule cells, leading to further sodium reabsorption.
* In the [[adrenal cortex]], angiotensin II 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. This increases blood volume and, therefore, increases blood pressure. In exchange for the reabsorbing of sodium to blood, [[potassium]] is secreted into the tubules, becomes part of urine and is excreted.
* Angiotensin II causes the 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. ADH also acts on the [[central nervous system]] to increase an individual's appetite for salt, and to stimulate the sensation of [[thirst]].
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These effects directly act together to increase blood pressure and are opposed by [[atrial natriuretic peptide]] (ANP).
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==Local renin–angiotensin systems==
Locally expressed renin–angiotensin systems have been found in a number of tissues, including the [[kidney]]s, [[adrenal gland]]s, the [[heart]], [[vasculature]] and [[nervous system]], and have a variety of functions, including [[Local blood flow regulation|local cardiovascular regulation]], in association or independently of the systemic renin–angiotensin system, as well as non-cardiovascular functions. Outside the kidneys, renin is predominantly picked up from the circulation but may be secreted locally in some tissues; its precursor prorenin is highly expressed in tissues and more than half of circulating prorenin is of extrarenal origin, but its physiological role besides serving as precursor to renin is still unclear. Outside the liver, angiotensinogen is picked up from the circulation or expressed locally in some tissues; with renin they form angiotensin I, and locally expressed [[angiotensin-converting enzyme]], [[chymase]] or other enzymes can transform it into angiotensin II. This process can be intracellular or interstitial.
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In the adrenal glands, it is likely involved in the [[paracrine]] regulation of [[aldosterone]] secretion; in the heart and vasculature, it may be involved in remodeling or vascular tone; and in the [[brain]], where it is largely independent of the circulatory RAS, it may be involved in local blood pressure regulation. In addition, both the [[central nervous system|central]] and [[peripheral nervous system|peripheral]] nervous systems can use angiotensin for sympathetic neurotransmission. Other places of expression include the reproductive system, the skin and digestive organs. Medications aimed at the systemic system may affect the expression of those local systems, beneficially or adversely.
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==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.
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==Clinical significance==
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[[File:Renin angiotensin aldosterone system.png|thumb|right|400px|Flowchart showing the clinical effects of RAAS activity and the sites of action of ACE inhibitors and angiotensin receptor blockers.]]
* [[ACE inhibitor]]s of angiotensin-converting enzyme inhibitors are often used to reduce the formation of the more potent angiotensin II. [[Captopril]] is an example of an ACE inhibitor. ACE cleaves a number of other peptides, and in this capacity is an important regulator of the [[kinin–kallikrein system]], as such blocking ACE can lead to side effects.
* [[Angiotensin II receptor antagonist]]s, also known as angiotensin receptor blockers, can be used to prevent angiotensin II from acting on its [[Angiotensin II receptor|receptors]].
* Direct [[renin inhibitor]]s can also be used for hypertension. The drugs that inhibit renin are [[aliskiren]] and the investigational [[remikiren]].
* [[Vaccine]]s against angiotensin II, for example [[CYT006-AngQb]], have been investigated.
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==See also==
* [[Discovery and development of angiotensin receptor blockers]]
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== Further reading ==
{{refbegin}}
* {{cite journal |vauthors=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=315–321 |year=1993 |pmid=8278677 |doi= 10.1007/BF02576239|s2cid=37700794 }}
{{refend}}
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==External links==
* {{MeshName|Renin-Angiotensin+System}}
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{{Cardiovascular physiology}}
{{renal physiology}}
{{Human homeostasis}}
{{Angiotensin receptor modulators}}
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{{二次利用|date=30 August 2023}}
{{DEFAULTSORT:Renin-Angiotensin System}}
[[Category:Human homeostasis]]
[[Category:Cardiovascular physiology]]
[[Category:Endocrinology]]
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