| Discovery | Angiotensin II is the active peptide hormone of the reninangiotensin system (RAS) with broad functions, includinga vasopressor effect and thirst stimulation. It is a drug targetfor hypertension and renal diseases. In 1940, two groups of researchers separately discovered a potent vasoconstrictor by incubating plasma withrenin; the substance was named both “angiotonin” and“hypertensin.” In 1958, they agreed to rename it“angiotensin” (angio=blood vessel; tensin=tension). |
| Structure | Ang II is a linear peptide with no known secondarymodification. Ang II is produced by the subsequent cleavage ofangiotensinogen (AGT) by renin and angiotensinI (Ang I) by ACE (See Renin Angiotensin System). Mr. 1046 of Ang II in humans. Freely soluble in water. |
| Gene, mRNA, and mRNA | AGT is located on chromosome 1q42.2 in humans. AGTbelongs to the SERPIN family A, member 8. AGT proteinsequences are highly variable but the functional domains(Ang I) are relatively conserved among vertebrates. Ang I sequences were identified by the incubation of a renin source (kidney extract) and an angiotensinogen source (plasma). Lamprey Ang I with sequenceNRVYVHPFTL was first sequenced using peptide purification. However, the lamprey genome data suggested adifferent Ang I sequence, and was later confirmed as thenative AGT. The purified teleost-type Ang I producedin the buccal gland was suggested to be involved in endocrine mimicry to reduce host immunorejection. |
| Agonist | A nonpeptide ligand, L-162,313 was shown to bind toAT1A, AT1B, and the AT2 receptor and act as an agoniston AT1A and AT1B receptors in mice (34.9 and 23.3% ofthe maximum response of Ang II, respectively). Earlystudies used CGP42112A as the agonist for the AT2receptor but compound 21, with little affinity for theAT1 receptor, was recently developed as a specific agonist of the AT2 receptor in humans. |
| Antagonist | Saralasin ([Sar1], [Ala8]-Ang II) is a partial agonist ofangiotensin II receptors, though it is commonly mistakenas a competitive antagonist. Antagonists including losartan, irbesartan, olmesartan, candesartan, and valsartanare commonly used clinically as AT1 blockers. TwoAT2 receptor antagonists, PD123177 (discontinued) andPD123319 (available), were developed to inhibit AT2activities. |
| Biological functions | Ang II/AT1 axis mediates vasoconstriction, thirst,release of vasopressin and aldosterone, renal sodiumreabsorption, fibrosis, inflammation, angiogenesis, vascular aging, and atherosclerosis. Ang II-induced effectsincluded blood pressure control; drinking; adrenergicstimulation; modulation of the ion pump and transporteractivities in the gill, kidney, and intestine in fish; controlof the filtering nephron population in fish; and regulation of ventral skin absorption in amphibians. The injection of Ang II significantly increased ventral skindrinking in the frog. Lamprey Ang II is a vasodepressorinstead of a vasopressor when injected intraarterially. The intracerebroventricular (ICV) injection of Ang II intothe trout increased the systemic blood pressure, heartrate, and ventilation rate. The ICV injection of Ang IIelicits tachycardia in contrast to bradycardia wheninjected peripherally. Central Ang II injection alsoinhibits the vagal-mediated baro-reflex, indicating thatbrain RAS is involved in the heart rate control.
The AT2 receptor is mostly embryonic. The expressiondecreases in adults and is confined in certain tissues suchas the kidney. The effects of AT2 are often antagonistic toAT1, and activation of the AT2 receptor usually indicatesa pathophysiological condition of AT1-mediated actionwith potential harmful consequences. AT2 is abundantlyexpressed in the spleen of the adult eel, which suggests animmune-related function. |
| Description | It is known that tumor tissues including metastatic lymph nodes are composed ofnewly growing vessels which lack blood flow autoregulation and are influenced onlysecondarily by the responding somatic vessels. Human angiotensin II (AT II). avasopressor, was introduced in Japan to improve the efficacy of systemicchemotherapy. In patients with various advanced cancers, i.v. infusion of AT II toachieve a mean blood pressure of 1.5 times of baseline (but not over 150 mm Hg)followed by a bolus injection of conventional cytotoxic agents increases blood flow5-7 fold in tumor tissues and therefore, increases drug delivery to the target tissueresulting in enhanced chemotherapeutic effects. This induced-hypertensionchemotherapy regimen can be performed safely with minimal side effects. |
| Description | Angiotensin II is a peptide hormone known best as a vasoconstrictor with central roles in chronic hypertension, heart failure, and stroke. It is an octapeptide typically generated by the removal of two residues from angiotensin I by angiotensin-converting enzyme (ACE). Angiotensin II is a ligand for at least two distinct receptors, AT1 and AT2, each evoking distinct signaling pathways and physiological responses. The development of antagonists for specific angiotensin II receptor subtypes represents a valuable alternative to ACE inhibitors. |
| Chemical Properties | White freeze-dried powder; soluble in water, soluble in methanol, ethanol and propylene glycol, insoluble in ethyl ether and chloroform; pH 5-8 in aqueous solution; stable in neutral solution, easily hydrolyzed when encountering strong acids and bases; amino acid sequence: aspartyl, argininyl, valerinyl, tyrosinyl, isoleucinyl, histidinyl, proline, phenylalanine. |
| Originator | Toa Eiyo (Japan) |
| Uses | Cardiopulmonary resuscitation - not yet an approved application |
| Uses | A peptide involved in the regulation of blood pressure |
| Uses | Angiotensin II is a peptide hormone known best as a vasoconstrictor with central roles in chronic hypertension, heart failure, and stroke. It is an octapeptide typically generated by the removal of two residues from angiotensin I by angiotensin-converting enzyme (ACE). Angiotensin II is a ligand for at least two distinct receptors, AT1 and AT2, each evoking distinct signaling pathways and physiological responses. The development of antagonists for specific angiotensin II receptor subtypes represents a valuable alternative to ACE inhibitors. |
| Definition | ChEBI: Ile(5)-angiotensin II is an angiotensin II that acts on the central nervous system (PDB entry: 1N9V). It has a role as a human metabolite. It is a tautomer of an Ile(5)-angiotensin II dizwitterion. |
| Brand name | Delivert |
| General Description | Functions in blood pressure maintenance. Stimulates the release of aldosterone from the adrenal gland. Has strong vasoconstrictive effects. Increases the entry of Ca2+ in heart muscle via voltage-sensitive channels and activates myosin light chain kinase. Activates JAK2 in smooth muscle cells. Activates p125FAK and a cytosolic 115-120 kDa calcium-dependent tyrosine kinase in rat epithelial cells. Also activates pp60c-src in vascular smooth muscle cells. Inhibits adenylate cyclase activity in spontaneously hypertensive rats. |
| Biochem/physiol Actions | Product does not compete with ATP. |
| Clinical Use | Renin antagonists, ACE inhibitors, and AT1 receptorblockers have been used, in singular or multiple blockade, to treat hypertension and other RAS-relateddiseases. High levels of Ang II are often related to hypertension,renal failure, and cardiac fibrosis. |
| in vitro | Most of the known actions of Angiotensin II (Ang II) are mediated by AT 1 receptors, the AT 2 receptor contributes to the regulation of blood pressure and renal function. Angiotensin II raises blood pressure (BP) by a number of actions, the most important ones being vasoconstriction, sympathetic nervous stimulation, increased aldosterone biosynthesis and renal actions. Other Angiotensin II actions include induction of growth, cell migration, and mitosis of vascular smooth muscle cells, increased synthesis of collagen type I and III in fibroblasts, leading to thickening of the vascular wall and myocardium, and fibrosis. These actions are mediated by type 1 Ang II receptors (AT 1 ). At the cellular level, responsiveness to Angiotensin II is conferred by the expression of the two classes of angiotensin receptors (AT 1 and AT 2 ). The effects of Angiotensin II to increase blood pressure are mediated by AT1 receptors. |
| in vivo | To distinguish the AT 1 receptor population that is critical for the pathogenesis of hypertension, osmotic minipumps are implanted s.c. into each animal to infuse Angiotensin II (1,000 ng/kg/min) continuously for 4 weeks. Angiotensin II causes hypertension by activating AT 1 receptors in the kidney promoting sodium reabsorption. |
| storage | -20°C (desiccate) |
