Everything about Angiotensinogen totally explained
and
1N9V
.
| PDB =
| Name = Angiotensinogen (serpin peptidase inhibitor, clade A, member 8)
| HGNCid = 333
| Symbol = AGT
| AltSymbols =; ANHU; SERPINA8
| OMIM = 106150
| ECnumber =
| Homologene = 14
| MGIid = 87963
| GeneAtlas_image1 = PBB_GE_AGT_202834_at_tn.png
| Function =
| Component =
| Process =
| Orthologs =
}}
Angiotensin is an
oligopeptide in the
blood that causes
vasoconstriction, increased
blood pressure, and release of
aldosterone from the
adrenal cortex. It 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.
Precursor, and types of angiotensin
Angiotensinogen
Angiotensinogen is an
α-2-globulin that's produced constitutively and released into the circulation mainly by the liver.
It is a member of the
serpin family, although it isn't 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 118 amino acids long, but other species have angiotensinogen of varying sizes
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. 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. 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).
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. 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.
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 contraction by an IP3-dependent mechanism).
ACE inhibitor drugs are major drugs against hypertension.
Other cleavage products of ACE, 7 or 9 amino acids long, are also known; they've differential affinity for
angiotensin receptors, although their exact role is still unclear. The action of angiotensin II itself is targeted by
angiotensin II receptor antagonists, which directly block
angiotensin II AT1 receptors.
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.
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.
Angiotensin II has prothrombotic potential through adhesion and aggregation of
platelets and production of
PAI-1 and
PAI-2.
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. 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 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. Elevated plasma angiotensin II levels are responsible for the elevated aldosterone levels present during the luteal phase of the
menstrual cycle.
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. 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. 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. 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.
Further Information
Get more info on 'Angiotensinogen'.
|
External Link Exchanges
Do you know how hard it is to get a link from a large encyclopaedia? Well we're different and will prove it. To get a link from us just add the following HTML to your site on a relevant page:
<a href="http://angiotensin.totallyexplained.com">Angiotensin Totally Explained</a>
Then simply click through this link from your web page. Our crawlers will verify your link, extract the title of your web page and instantly add a link back to it. If you like you can remove the words Totally Explained and embed the link in article text.
As long as your link remains in place, we'll keep our link to you right here. Please play fair - our crawlers are watching. Your site must be closely related to this one's topic. Any kind of spamming, dubious practises or removing the link will result in your link from us being dropped and, potentially, your whole site being banned. |
