Salt Fractionation Of Plasma Proteins

Salt Fractionation Of Plasma Proteins

Angiotensin   by jekky

Precursor, and types of angiotensin

Angiotensinogen

Angiotensinogen is an -2-globulin that is produced constitutively and released into the circulation mainly by the liver. It is a member of the serpin family, 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 452 amino acids long, but other species have angiotensinogen of varying sizes. The first 12 amino acids are the most important for activity.

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile

Angiotensin I

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu

Renin-angiotensin-aldosterone system

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 2.

Angiotensin II

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe

Angiotensin I is converted to angiotensin II through removal of two C-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 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, whereas, in tissue, it may be as long as 1530 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 that, 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

They are potent direct vasoconstrictors, 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 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.

Neural effects

Angiotensin III 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+ 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 as 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.

Renal effects of Angiotensin II

Target

Action

Mechanism

Renal artery &

afferent arterioles

vasoconstriction

VDCCs Ca2+ influx

efferent arteriole

vasoconstriction

(probably) activate Angiotensin receptor 1 Activation of Gq LC activity P3 and DAG activation of IP3 receptor in SR ntracellular Ca2+

mesangial cells

contraction iltration area

activation of Gq LC activity P3 and DAG activation of IP3 receptor in SR ntracellular Ca2+

VDCCs Ca2+ influx

Tubuloglomerular feedback

Increased sensitivity

Increase in afferent arteriole responsiveness to signals from macula densa

medullary blood flow

Reduction

See also

ACE inhibitor

Angiotensin receptor

Angiotensin II receptor antagonist

References

^ Basso N, Terragno NA (December 2001). “History about the discovery of the renin-angiotensin system”. Hypertension 38 (6): 12469. doi:10.1161/hy1201.101214. PMID 11751697. http://hyper.ahajournals.org/cgi/pmidlookup?view=long&pmid=11751697. 

^ NCBI HomePage

^ Physiology at MCG 7/7ch09/7ch09p16

^ Skurk T, Lee YM, Hauner H (May 2001). “Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture”. Hypertension 37 (5): 133640. PMID 11358950. http://hyper.ahajournals.org/cgi/pmidlookup?view=long&pmid=11358950. 

^ Gesualdo L, Ranieri E, Monno R, et al. (August 1999). “Angiotensin IV stimulates plasminogen activator inhibitor-1 expression in proximal tubular epithelial cells”. Kidney Int. 56 (2): 46170. doi:10.1046/j.1523-1755.1999.00578.x. PMID 10432384. 

^ Unless else specified in table, then ref is: Walter F., PhD. Boron (2005). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3.  Page 771

Further reading

de Gasparo M, Catt KJ, Inagami T, “et al.” (2000). “International union of pharmacology. XXIII. The angiotensin II receptors”. Parmacol Rev. 52: 415472. 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

Lees KR, MacFadyen RJ, Doig JK, Reid JL (1993). “Role of angiotensin in the extravascular system”. Journal of human hypertension 7 Suppl 2: S712. PMID 8230088. 

Weir MR, Dzau VJ (2000). “The renin-angiotensin-aldosterone system: a specific target for hypertension management”. Am. J. Hypertens. 12 (12 Pt 3): 205S213S. doi:10.1016/S0895-7061(99)00103-X. PMID 10619573. 

Berry C, Touyz R, Dominiczak AF, et al. (2002). “Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide”. Am. J. Physiol. Heart Circ. Physiol. 281 (6): H233765. PMID 11709400. 

Sernia C (2002). “A critical appraisal of the intrinsic pancreatic angiotensin-generating system”. JOP 2 (1): 505. PMID 11862023. 

Varagic J, Frohlich ED (2003). “Local cardiac renin-angiotensin system: hypertension and cardiac failure”. J. Mol. Cell. Cardiol. 34 (11): 143542. doi:10.1006/jmcc.2002.2075. PMID 12431442. 

Wolf G (2006). “Role of reactive oxygen species in angiotensin II-mediated renal growth, differentiation, and apoptosis”. Antioxid. Redox Signal. 7 (9-10): 133745. doi:10.1089/ars.2005.7.1337. PMID 16115039. 

Cazaubon S, Deshayes F, Couraud PO, Nahmias C (2006). “[Endothelin-1, angiotensin II and cancer]“. Med Sci (Paris) 22 (4): 41622. PMID 16597412. 

Ariza AC, Bobadilla NA, Halhali A (2007). “[Endothelin 1 and angiotensin II in preeeclampsia]“. Rev. Invest. Clin. 59 (1): 4856. PMID 17569300. 

External links

MeSH Angiotensins

v  d  e

Cardiovascular system, physiology: cardiovascular physiology

Heart

Volumes

Stroke volume = End-diastolic volume End-systolic volume

Cardiac output = Heart rate Stroke volume

Afterload  Preload

Frank-Starling law of the heart  Cardiac function curve  Venous return curve

Aortic valve area calculation  Ejection fraction  Cardiac index

Interaction diagrams

Cardiac cycle  Wiggers diagram  Pressure volume diagram

Tropism

Chronotropic (Heart rate)  Dromotropic (Conduction velocity)  Inotropic (Contractility)  Batmotropic (Excitability)  Lusitropic (Relaxation)

Conduction system /

Cardiac electrophysiology

Cardiac action potential (Atrial action potential, Ventricular action potential)  Effective refractory period  Pacemaker potential  EKG (P wave, PR interval, QRS complex, QT interval, ST segment, T wave, U wave)  Hexaxial reference system

Chamber pressure

Central venous pressure/right atrial pressure Right ventricular pressure Pulmonary artery pressure Pulmonary wedge pressure/left atrial pressure Left ventricular pressure Aortic pressure

Other

Ventricular remodeling

Vascular system/

Hemodynamics

Blood flow

Compliance  Vascular resistance (Total peripheral resistance)  Pulse  Perfusion

Blood pressure

Pulse pressure (Systolic – Diastolic)  Mean arterial pressure

Jugular venous pressure

Portal venous pressure

Regulation of BP

Baroreflex  Kinin-kallikrein system  Renin-angiotensin system  Vasoconstrictors/Vasodilators  Autoregulation (Myogenic mechanism, Tubuloglomerular feedback)  Paraganglia (Aortic body, Carotid body, Glomus cell)

heart navs: anat/physio/dev, noncongen/congen/neoplasia, symptoms+signs/eponymous, proc

vascular navs: anat/physio/dev, noncongen/systemic vasculitis/congen/neoplasia, symptoms+signs/eponymous, proc

v  d  e

Peptides: neuropeptides

Hypothalamic

Somatostatin  CRH  GnRH  GHRH  Orexins  TRH  POMC (ACTH  MSH  Lipotropin)

Gastrointestinal hormones

Cholecystokinin  Gastric inhibitory polypeptide  Gastrin  Motilin  Secretin  Vasoactive intestinal peptide

Other hormones

Calcitonin  Oxytocin  Vasopressin

Other neuropeptides

Angiotensin  Bombesin  Calcitonin gene-related peptide  Carnosine  Cocaine and amphetamine regulated transcript  Delta sleep-inducing peptide  FMRFamide  Galanin  Galanin-like peptide  Gastrin releasing peptide  Kinins (Bradykinin  Tachykinins)  Neuropeptide S  Neuropeptide Y  Neurophysins  Neurotensin  Pancreatic polypeptide  Pituitary adenylate cyclase activating peptide  VGF

Neuromedins

B  N  S  U

Opioid peptides

Dynorphin  Endomorphin  Endorphin  Enkephalin  Nociceptin  Opiorphin

v  d  e

Autacoids

Kinins

Kininogen (HMWK, LMWK)  Bradykinin  Kallidin  Tachykinins  Urotensin-II

Others

Angiotensin  Eicosanoid  Histamine  Platelet-activating factor  Serotonin

Categories: Human proteins | Peptide hormones | Cardiovascular system | Endocrinology | Physiology

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