Angiotensin: Encyclopedia - Angiotensin

Angiotensin

Angiotensinogen, angiotensin I (CAS# 9041-90-1) and angiotensin II (CAS# 11128-99-7) are peptides involved in maintenance of blood volume and pressure. They play an important role in the renin-angiotensin system.

Angiotensin - Angiotensinogen

Angiotensinogen is the precursor molecule, and it is produced constitutively and released into the circulation mainly by the liver although other sites have been thought to contribute to local effects of the molecule. Biochemically it is a member of the protein family of serpins (although it is not, like other serpins, known to inhibit other enzymes).

Production of the peptide is increased by corticosteroids, estrogens, thyroid hormones, and notably, angiotensin II.

In humans, the peptide sequence for angiotensinogen is 453 amino acids long.

When blood pressure decreases in the kidneys, they produce an enzyme called renin. Renin cleaves the peptide bond between the leucine (Leu) and the valine (Val) residues creating the ten amino acid peptide angiotensin I.

Angiotensin - Angiotensin I

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

Angiotensin I has little biological effect. Its main role is to become angiotensin II, by removal of two of the terminal residues.

to Angiotensin III via an intermediate (des-Asp) Angiotensin I.

Angiotensin - Angiotensin II

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

The main enzyme that cleaves Angiotensin I to Angiotensin II is called Angiotensin-converting enzyme (ACE, also known as kininase) and is found predominantly in the lungs. This enzyme is a target for drugs (ACE inhibitors) that inactivate it, decreasing the rate of angiotensin II production. Other splice products of 7 or 9 amino acids are also known; they have differential affinity for angiotensin receptors, although their exact role is as yet unclear.

This eight amino acid long molecule has a number of effects throughout the body.

Angiotensin - Effects of Angiotensin II

Angiotensin - Vascular

It is a potent direct vasoconstrictor, causing arteries and veins to constrict and so leading to an increase in blood pressure. It also potentiates the release of norepinephrine by a direct action on postganglionic sympathetic fibres.

Angiotensin - Brain

Angiotensin II acts on the brain to increase the sense of thirst via the subfornical organ (SFO), decrease the response of the baroreceptor reflex and increase the desire for salt. It also increases the secretion of vasopressin and ACTH.

Angiotensin - Adrenals

It acts on the adrenal cortex, causing it to release aldosterone, a hormone that causes the kidneys to retain sodium and lose potassium.

Angiotensin - Renal

It has a direct effect on the proximal tubules to increase Na+ resorption, and although it contracts mesangial cells due to increased sympathetic effects, its overall effect is to increase the glomerular filtration rate by increasing the renal perfusion pressure.

Angiotensin - Other

It has been thought that angiotensin II could be a cause of cardiac muscle hypertrophy (when the heart wall grows bigger).

Angiotensin II has prothrombothic potential through adhesion and aggregation of platelets and production of PAI-1 and PAI-2.

Angiotensin II is degraded by angiotensinases that are located in red blood cells and the vascular beds of most tissues, and has a half-life in humans of 1-2 minutes. It is degraded to Angiotensin III.

Angiotensin - Angiotensin III & IV

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, a hexapeptide also has some activity.

See also

• Angiotensin receptor
• Angiotensin II receptor antagonist

Adapted from the Wikipedia article "Angiotensin", under the G.N U Free Docmentation License. Please also see http://en.wikipedia.org/wiki