Angiotensin
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Angiotensin is a polypeptide in the blood that causes vasoconstriction, increased blood pressure, and aldosterone release from the adrenal cortex. 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.
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Angiotensinogen
Angiotensinogen is an α-2-globulin that is produced constitutively and released into the circulation mainly by the liver, although other sites are thought to be involved also. 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 consist of 453 amino acid residues.
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 JG 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 the 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 by removal of two terminal residues by the enzyme Angiotensin-converting enzyme (ACE, or kininase), which is found predominantly in pulmonary capillaries.
ACE is a target for inactivation by ACE inhibitor drugs, which decrease the rate of angiotensin II production. Other cleavage products, 7 or 9 amino acids long, are also known; they have differential affinity for angiotensin receptors, although their exact role is still unclear.
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 humans of 1-2 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 of Angiotensin
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.
It has been thought that angiotensin II could be a cause of cardiac muscle hypertrophy (when the heart wall grows bigger).
Neural Effects
Angiotensin II increases thirst sensation through the subfornical organ (SFO) of the brain, decreases the response of the baroreceptor reflex, and increases the desire for salt. It increases the secretion of ADH in the posterior pituitary and 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 elevated aldosterone levels during the luteal phase of the menstrual cycle.
Renal Effects
Angiotensin II has a direct effect on the proximal tubules to increase Na+ resorption. Although it slightly inhibits glomerular filtration by indirectly (through sympathetic effects) and directly stimulating mesangial cell constriction, its overall effect is to increase the glomerular filtration rate by increasing the renal perfusion pressure via efferent renal constriction.
See also
References
- 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.de:Angiotensin
fr:Angiotensine nl:Angiotensine pl:Angiotensyna pt:Angiotensina II