Angiotensinogen, angiotensin I and angiotensin II are peptides involved in maintenance of blood volume and pressure. They play an important role in the renin-angiotensin system.

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 homones, and notably, angiotensin II.

In humans, the peptide sequence for angiotensinogen is 485 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. The ten amino acid peptide angiotensin I is created:

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

Angiotensin I

Angiotensin I has little biological effect. Its main role is to become angiotensin II.

Angiotensin I is a ten amino acid peptide. When the last two amino acids are removed, it becomes angiotensin II.

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

The main enzyme that cleaves this precursor is called Angiotensin-converting enzyme (ACE, also known as kininase). 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 angiontensin receptors, although their exact role is as yet unclear.

Angiotensin II

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

It is a potent vasoconstrictor, causing arteries and veins to constrict. The constriction of these vessels will push up blood pressure. This is done through release of noradrenaline, adrenaline, aldosterone, vasopressin and endothelin 1 .

Angiotensin II also acts on the brain to increase the sense of thirst, and increase the desire for salt. It also increases the secretion of vasopressin and ACTH.

It acts on the adrenal cortex, causing it to produce aldosterone, a chemical that causes the kidneys to retain sodium, and lose potassium. As well as this, it is thought to directly work on the kidneys to increase sodium resorption at the proximal tubules.

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 platlets and production of PAI-1 and PAI-2 .

Angiotensin II is destroyed by angiotensinases that are located in the vascular beds of most tissues.

See also

• Angiotensin receptor
• Angiotensin II receptor antagonist