- Angiotensinogen is an α-2-globulin that is produced constitutively and released into the circulation mainly by the liver.
- Plasma angiotensinogen levels are increased by plasma corticosteroid, estrogen, thyroid hormone, and angiotensin II levels.
Angiotensin I 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 angiotensin I. Angiotensin I appears to have no biological activity and exists solely as a precursor to angiotensin 2.
Angiotensin I is converted to angiotensin II through removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE, or kinase), which is found predominantly in the capillaries of the lung. ACE is actually found all over the body, but has its highest density in the lung due to the high density of capillary beds there. Angiotensin II acts as an endocrine, autocrine/paracrine, and intracrine hormone.
ACE is a target for inactivation by ACE inhibitor drugs, which decrease the rate of angiotensin II production. Angiotensin II increases blood pressure by stimulating the Gq protein in vascular smooth muscle cells. ACE inhibitor drugs are major drugs against hypertension.