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Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23304450 | https://clinicaltrials.gov/ct2/show/NCT00711789 | https://www.ncbi.nlm.nih.gov/pubmed/26254369 | https://www.ncbi.nlm.nih.gov/pubmed/20146480

Angiotensin is a peptide hormone that causes vasoconstriction and a subsequent increase in blood pressure. It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone, from the adrenal cortex. Aldosterone promotes sodium retention in the distal nephron, in the kidney, which also drives blood pressure up. Angiotensin is an oligopeptide and is a hormone and a powerful dipsogen. Angiotensin I is derived from the precursor molecule angiotensinogen, a serum globulin produced in the liver. Angiotensin I is converted to angiotensin II (AII) through removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE), primarily through ACE within the lung (but also present in endothelial cells and kidney epithelial cells). ACE found in other tissues of the body has no physiological role (ACE has a high density in the lung, but activation here promotes no vasoconstriction, angiotensin II is below physiological levels of action). Angiotensin II acts as an endocrine, autocrine/paracrine, and intracrine hormone. Angiotensin II has prothrombotic potential through adhesion and aggregation of platelets and stimulation 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 α1 adrenoreceptors. Angiotensin II increases thirst sensation (dipsogen) through the subfornical organ of the brain, decreases the response of the baroreceptor reflex, and increases the desire for salt. It increases secretion of ADH in the posterior pituitary and secretion of ACTH in the anterior pituitary. It also potentiates the release of norepinephrine by direct action on postganglionic sympathetic fibers. Angiotensin II acts on the adrenal cortex, causing it to release aldosterone, a hormone that causes the kidneys to retain sodium and lose potassium. Elevated plasma angiotensin II levels are responsible for the elevated aldosterone levels present during the luteal phase of the menstrual cycle. Angiotensin II has a direct effect on the proximal tubules to increase Na+ reabsorption. It has a complex and variable effect on glomerular filtration and renal blood flow depending on the setting. Increases in systemic blood pressure will maintain renal perfusion pressure; however, constriction of the afferent and efferent glomerular arterioles will tend to restrict renal blood flow. The effect on the efferent arteriolar resistance is, however, markedly greater, in part due to its smaller basal diameter; this tends to increase glomerular capillary hydrostatic pressure and maintain glomerular filtration rate. A number of other mechanisms can affect renal blood flow and GFR. High concentrations of Angiotensin II can constrict the glomerular mesangium, reducing the area for glomerular filtration. Angiotensin II is a sensitizer to tubuloglomerular feedback, preventing an excessive rise in GFR. Angiotensin II causes the local release of prostaglandins, which, in turn, antagonize renal vasoconstriction. The net effect of these competing mechanisms on glomerular filtration will vary with the physiological and pharmacological environment. 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.

CNS Activity

Curator's Comment: Although the blood-brain barrier is impermeable for all renin-angiotensin system components, the local brain renin-angiotensin system has possible physiological and pharmacological functions in the neuronal system

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.9 nM [Ki]
0.23 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
GIAPREZA

Approved Use

GIAPREZA is a vasoconstrictor to increase blood pressure in adults with septic or other distributive shock.

Launch Date

2017
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Preliminary biochemical characterization of two angiotensin II receptor subtypes.
1989 Aug 30
Human angiotensin receptor subtypes.
1994 Jan
The in vivo metabolism of cholecystokinin (CCK-8) is essentially ensured by aminopeptidase A.
1996
Identification of metabolic pathways of brain angiotensin II and III using specific aminopeptidase inhibitors: predominant role of angiotensin III in the control of vasopressin release.
1996 Oct 15
Distinction between surmountable and insurmountable selective AT1 receptor antagonists by use of CHO-K1 cells expressing human angiotensin II AT1 receptors.
1999 Feb
Enzymatic properties of human aminopeptidase A. Regulation of its enzymatic activity by calcium and angiotensin IV.
2006 Aug 18
Patents

Sample Use Guides

Angiotensin II will be given by continuous infusion for 24 hours starting at a dose of 5ng/kg/min and then titrated to a maximum dose of 15 ng/kg/min according to a blood pressure based protocol
Route of Administration: Intravenous
HepG2 or siRNAs-transfected HepG2 cells in the logarithmic phase were digested and centrifuged to collect the cells. Then, the cells were seeded into 96-well culture plates at a density of 5000 cells per well in triplicate for each group. The cells were cultured with fresh medium containing TNF-α and Ang II (1nM, 10 nM, 100nM 1mkM, 10 mkM) alone or in combination at the specified concentrations. After treatment for 12, 24 and 48 h, 10 μl of CCK-8 reagent (Dojindo, Kumamoto, Japan) was added to each well, and the plates were incubated for another 1 h at 37 °C. The absorbance was measured at 450 nm using an Infinite M1000 PRO microplate reader (Tecan, Mannedorf, Switzerland).
Substance Class Protein
Created
by admin
on Sat Dec 16 09:55:07 GMT 2023
Edited
by admin
on Sat Dec 16 09:55:07 GMT 2023
Protein Type PEPTIDE
Protein Sub Type
Sequence Type COMPLETE
Record UNII
31L3HS630A
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ANGIOTENSIN II ACETATE
USAN  
USAN  
Official Name English
ANGIOTENSIN II, 5-L-ISOLEUCINE-, ACETATE (SALT)
Systematic Name English
ANGIOTENSIN II ACETATE [ORANGE BOOK]
Common Name English
Angiotensin II acetate [WHO-DD]
Common Name English
HUMAN ANGIOTENSIN II ACETATE SALT
Common Name English
ANGIOTENSIN II TRIACETATE
Common Name English
ASP-ARG-VAL-TYR-ILE-HIS-PRO-PHE ACETATE
Common Name English
ANGIOTENSIN II ACETATE HUMAN
Common Name English
ANGIOTENSIN II ACETATE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C307
Created by admin on Sat Dec 16 09:55:07 GMT 2023 , Edited by admin on Sat Dec 16 09:55:07 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID801027704
Created by admin on Sat Dec 16 09:55:07 GMT 2023 , Edited by admin on Sat Dec 16 09:55:07 GMT 2023
PRIMARY
RXCUI
2204740
Created by admin on Sat Dec 16 09:55:07 GMT 2023 , Edited by admin on Sat Dec 16 09:55:07 GMT 2023
PRIMARY
USAN
DE-135
Created by admin on Sat Dec 16 09:55:07 GMT 2023 , Edited by admin on Sat Dec 16 09:55:07 GMT 2023
PRIMARY
PUBCHEM
172197
Created by admin on Sat Dec 16 09:55:07 GMT 2023 , Edited by admin on Sat Dec 16 09:55:07 GMT 2023
PRIMARY
FDA UNII
31L3HS630A
Created by admin on Sat Dec 16 09:55:07 GMT 2023 , Edited by admin on Sat Dec 16 09:55:07 GMT 2023
PRIMARY
NCI_THESAURUS
C142924
Created by admin on Sat Dec 16 09:55:07 GMT 2023 , Edited by admin on Sat Dec 16 09:55:07 GMT 2023
PRIMARY
CAS
68521-88-0
Created by admin on Sat Dec 16 09:55:07 GMT 2023 , Edited by admin on Sat Dec 16 09:55:07 GMT 2023
NON-SPECIFIC STOICHIOMETRY
DRUG BANK
DBSALT002093
Created by admin on Sat Dec 16 09:55:07 GMT 2023 , Edited by admin on Sat Dec 16 09:55:07 GMT 2023
PRIMARY
Related Record Type Details
STARTING MATERIAL -> INGREDIENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
MOL_WEIGHT:NUMBER(CALCULATED) CHEMICAL
Molecular Formula CHEMICAL