Angiotensin causes blood vessels to constrict, and drives blood pressure up. It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also creates aldosterone, which causes the tubules of the kidneys to retain sodium and water, which also drives blood pressure up.
Angiotensin is an oligopeptide in the
bloodthat causes vasoconstriction, increased blood pressure, and release of aldosteronefrom the adrenal cortex. It is a hormoneand 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 Clinicand Cibalaboratories in Basel, Switzerland. [cite journal |author=Basso N, Terragno NA |title=History about the discovery of the renin-angiotensin system |journal=Hypertension |volume=38 |issue=6 |pages=1246–9 |year=2001 |month=December |pmid=11751697 |doi= |url=http://hyper.ahajournals.org/cgi/pmidlookup?view=long&pmid=11751697]
Precursor, and types of angiotensin
Angiotensinogen is an α-2-globulin that is produced constitutively and released into the circulation mainly by the liver.It is a member of the
serpinfamily, 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 118 amino acids long, but other species have angiotensinogen of varying sizes [ [http://www.ncbi.nlm.nih.gov NCBI HomePage ] ]
Angiotensin I (CAS# 11128-99-7) is formed by the action of
reninon 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 bondbetween the leucine(Leu) and valine(Val) residues on angiotensinogen, creating the ten amino acidpeptide (des-Asp) angiotensin I (CAS# 9041-90-1).
Angiotensin I appears to have no biological activity and exists solely as a precursor to angiotensin 2.
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. [GeorgiaPhysiology|7/7ch09/7ch09p16] 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 intracrinehormone.
ACE is a target for inactivation by
ACE inhibitordrugs, 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 inhibitordrugs are major drugs against hypertension.
Other cleavage products of ACE, 7 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 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.
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.
Arg | Val-Tyr-Ile-His-Pro-Phe
Angiotensin IV is a hexapeptide which, like angiotensin III, has some lesser activity.
Renin-angiotensin_system#Effects"Angiotensins II, III & IV have a number of effects throughout the body:
It is a potent direct
vasoconstrictor, constricting arteries and veins and increasing blood pressure.
Angiotensin II has prothrombotic potential through adhesion and aggregation of
plateletsand production of PAI-1 and PAI-2.cite journal |author=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 |year=2001 |month=May |pmid=11358950 |doi= |url=http://hyper.ahajournals.org/cgi/pmidlookup?view=long&pmid=11358950] cite journal |author=Gesualdo L, Ranieri E, Monno R, "et al" |title=Angiotensin IV stimulates plasminogen activator inhibitor-1 expression in proximal tubular epithelial cells |journal=Kidney Int. |volume=56 |issue=2 |pages=461–70 |year=1999 |month=August |pmid=10432384 |doi=10.1046/j.1523-1755.1999.00578.x |url=] 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 A1 adrenoreceptors.
Angiotensin II increases
thirstsensation ( 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 pituitaryand secretion of ACTH in the anterior pituitary. It also potentiates the release of norepinephrineby direct action on postganglionic sympathetic fibers.
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.
Angiotensin II has a direct effect on the proximal tubules to increase Na+
absorption. It has a complex and variable effect on glomerular filtrationand renal blood flowdepending 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 sensitizer to Tubuloglomerular feedbackpreventing 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.
Angiotensin II receptor antagonist
*"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, 2001PBB_Further_reading
*cite journal | author=Lees KR, MacFadyen RJ, Doig JK, Reid JL |title=Role of angiotensin in the extravascular system |journal=Journal of human hypertension |volume=7 Suppl 2 |issue= |pages= S7–12 |year= 1993 |pmid= 8230088 |doi=
*cite journal | author=Weir MR, Dzau VJ |title=The renin-angiotensin-aldosterone system: a specific target for hypertension management |journal=Am. J. Hypertens. |volume=12 |issue= 12 Pt 3 |pages= 205S–213S |year= 2000 |pmid= 10619573 |doi=
*cite journal | author=Berry C, Touyz R, Dominiczak AF, "et al." |title=Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide |journal=Am. J. Physiol. Heart Circ. Physiol. |volume=281 |issue= 6 |pages= H2337–65 |year= 2002 |pmid= 11709400 |doi=
*cite journal | author=Sernia C |title=A critical appraisal of the intrinsic pancreatic angiotensin-generating system |journal=JOP |volume=2 |issue= 1 |pages= 50–5 |year= 2002 |pmid= 11862023 |doi=
*cite journal | author=Varagic J, Frohlich ED |title=Local cardiac renin-angiotensin system: hypertension and cardiac failure |journal=J. Mol. Cell. Cardiol. |volume=34 |issue= 11 |pages= 1435–42 |year= 2003 |pmid= 12431442 |doi=
*cite journal | author=Wolf G |title=Role of reactive oxygen species in angiotensin II-mediated renal growth, differentiation, and apoptosis |journal=Antioxid. Redox Signal. |volume=7 |issue= 9-10 |pages= 1337–45 |year= 2006 |pmid= 16115039 |doi= 10.1089/ars.2005.7.1337
*cite journal | author=Cazaubon S, Deshayes F, Couraud PO, Nahmias C |title= [Endothelin-1, angiotensin II and cancer] |journal=Med Sci (Paris) |volume=22 |issue= 4 |pages= 416–22 |year= 2006 |pmid= 16597412 |doi=
*cite journal | author=Ariza AC, Bobadilla NA, Halhali A |title= [Endothelin 1 and angiotensin II in preeeclampsia] |journal=Rev. Invest. Clin. |volume=59 |issue= 1 |pages= 48–56 |year= 2007 |pmid= 17569300 |doi=
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Look at other dictionaries:
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