Angiotensin

Angiotensinogen
Identifiers
Symbol(s)	AGT
Entrez	183
OMIM	106150
RefSeq	NM_000029
UniProt	P01019
Other data
Locus	Chr. 1 q41-qter

Angiotensin is an oligopeptide hormone that circulates in the blood and which causes vasoconstriction, increased blood pressure, and release of aldosterone from the adrenal cortex. It is also a powerful dipsogen as a result of its actions on the brain. 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.

Renin-angiotensin-aldosterone system

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 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.

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 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 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) 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 angiotensin

Angiotensins II, III & IV have a number of effects 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).

• 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.

• 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 during the luteal phase of the menstrual cycle.

• 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.