Angiotensin is an oligopeptide in the blood that causes vasoconstriction, increased blood pressure, and release of aldosterone from the adrenal cortex. It is a hormone and a powerful dipsogen. 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. Angiotensin was independently isolated in Indianapolis and Argentina in the late 1930s (as 'Angiotonin' and 'Hypertensin' respectively) and subsequently characterised and synthesized by groups at the Cleveland Clinic and Ciba laboratories in Basel, Switzerland.
Angiotensinogen is also known as renin substrate.
Human angiotensinogen is 118 amino acids long, but other species have angiotensinogen of varying sizes
Angiotensin I (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.
Angiotensin I appears to have no biological activity and exists solely as a precursor to angiotensin 2.
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 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 (which in turn activates contraction by an IP3-dependent mechanism). ACE inhibitor drugs are major drugs against hypertension.
Other cleavage products of ACE, 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.
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.
Arg | Val-Tyr-Ile-His-Pro-Phe
Angiotensin IV is a hexapeptide which, like angiotensin III, has some lesser activity.
Angiotensin II has prothrombotic potential through adhesion and aggregation of platelets and production of PAI-1 and PAI-2.
When cardiac cell growth is stimulated, a local (autocrine-paracrine) renin-angiotensin system is activated in the cardiac myocyte, which stimulates cardiac cell growth through Protein Kinase C. The same system can be activated in smooth muscle cells in conditions of hypertension, atherosclerosis or endothelial damage. Angiotensin II is the most important Gq stimulator of the heart during hypertrophy, compared to endothelin-1 and A1 adrenoreceptors.
|Renal artery & |
|vasoconstriction||VDCCs --> Ca2+ influx|
|efferent arteriole||vasoconstriction||(probably) activate Angiotensin receptor 1 --> Activation of Gq --> ↑PLC activity --> ↑IP3 and DAG --> activation of IP3 receptor in SR --> ↑intracellular Ca2+|
|mesangial cells||contraction --> ↓filtration area|
|Tubuloglomerular feedback||Increased sensitivity||Increase in afferent arteriole responsiveness to signals from macula densa|
|medullary blood flow||Reduction|