From Citizendium
Jump to navigation Jump to search
This article is developed but not approved.
Main Article
Related Articles  [?]
Bibliography  [?]
External Links  [?]
Citable Version  [?]
This editable, developed Main Article is subject to a disclaimer.
Symbol(s) AGT
Entrez 183
OMIM 106150
RefSeq NM_000029
UniProt P01019
Other data
Locus Chr. 1 q41-qter

The angiotensins circulate in the blood and are "oligopeptides which are important in the regulation of blood pressure (vasoconstriction) and fluid homeostasis via the renin-angiotensin system. These include angiotensins derived naturally from precursor angiotensinogen, and those synthesized".[1]

The angiotensins also cause release of aldosterone from the adrenal cortex and are powerful dipsogen as a result of actions on the brain.


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 concentrations of angiotensinogen are increased by plasma corticosteroid, estrogen, thyroid hormone, and angiotensin II levels. Angiotensinogen has 453 amino acid residues.

Angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) (CAS# 11128-99-7) is formed by the action of the enzyme 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 decapeptide (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 (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe | His-Leu).

Angiotensin II is produced from angiotensin I through removal of two terminal residues by the enzyme Angiotensin-converting enzyme (ACE, or kininase), which is found predominantly in the capillaries of the lung. ACE is a target for inactivation by ACE inhibitor drugs, which reduce 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. 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 the systemic circulation of about 30 seconds, but in tissue, it may be as long as 15-30 minutes.

Angiotensin III (Asp | Arg-Val-Tyr-Ile-His-Pro-Phe) 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) is a hexapeptide which, like angiotensin III, has some lesser activity.

Effects of angiotensins

Angiotensin I has relatively little activity, but angiotensin II has a variety of physiologically important actions:

  • Throughout the body, angiotensin II is a potent direct vasoconstrictor, constricting arteries and veins and increasing blood pressure. It also has prothrombotic potential through adhesion and aggregation of platelets and production of PAI-1 and PAI-2. It has been proposed that angiotensin II could be a cause of vascular and cardiac muscle hypertrophy (enlargement of the heart).
  • In the kidneys, it constricts glomerular arterioles, having a greater effect on efferent arterioles than on afferent arterioles. As with most other capillary beds in the body, the constriction of afferent arterioles increases the arterioler resistance, raising 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 buildup 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. Angiotensin II has a direct effect on the proximal tubules to increase resorption of sodium. 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.
  • Angiotensin II increases thirst( is a potent dipsogen) through its actions on the subfornical organ, one of the circumventricular organs of the brain; it also decreases the response of the baroreceptor reflex, and it increases the salt appetite¦desire for salt. It increases the secretion of vasopressin from the posterior pituitary and of ACTH from the anterior pituitary. It also potentiates the release of norepinephrine by direct action on postganglionic sympathetic fibers.
  • Angiotensin II acts on the adrenal cortex to cause the release of the mineralocorticoid hormone aldosterone. Aldosterone acts on the tubules (i.e. the distal convoluted tubules and the cortical collecting ducts) in the kidneys, causing them to reabsorb more sodium and water from the urine. Potassium is secreted into the tubule in exchange for the sodium, which is reabsorbed. Aldosterone also acts on the central nervous system to increase a person's appetite for salt, and to make them feel thirsty.Elevated plasma angiotensin II levels are responsible for the elevated aldosterone levels during the luteal phase of the menstrual cycle.

These effects directly act to increase the amount of fluid in the blood, making up for a loss in volume, and to increase blood pressure.

Clinical significance

The renin-angiotensin system is often manipulated clinically to treat hypertension and heart failure. Angiotensin-converting enzyme inhibitors (ACE inhibitors) are often used to reduce the formation of the more potent angiotensin II. Alternatively, angiotensin receptor blockers can be used to prevent angiotensin II from acting on angiotensin receptors.

Interestingly, ACE cleaves a number of other peptides, and in this capacity is an important regulator of the kallikrein-kinin system.