Peptide Basics
Angiotensin: Angiotensin I and II, the Renin-Angiotensin System, ACE2 and What FDA Records Show
Angiotensin is a family of small peptide hormones cut from a liver protein, angiotensinogen; its main active form, angiotensin II, narrows blood vessels and makes the body hold salt and water, which raises blood pressure. This page sets out how one precursor yields eight angiotensins, how renin and ACE turn it on, what the AT1 and AT2 receptors do, how ACE2 and angiotensin 1-7 counterbalance it, and which medicines in FDA’s records act on the system, including angiotensin II itself. Every figure is taken from UniProt, PubChem, MeSH, PubMed or FDA’s own databases and labels.
What angiotensin is
MeSH, the U.S. National Library of Medicine’s subject index, describes the angiotensins as oligopeptides that are important in the regulation of blood pressure, by narrowing blood vessels, and of fluid balance, through the renin-angiotensin system. They are peptide hormones, and very short ones: the longest has ten amino acids.
Their source is a much larger protein, angiotensinogen. UniProt records that it is made by the liver and released into the blood, and MeSH adds that the liver produces it in response to lowered blood pressure. Angiotensinogen itself is inactive; the angiotensins are cut from it by a series of enzymes.
The name was settled in print in 1958, when Braun-Menéndez and Page published “Suggested revision of nomenclature: angiotensin” in Science (PMID 17750687; PubMed holds no abstract, so we cite it by title). Papers from two years earlier still use an older name, hypertensin: Skeggs and colleagues showed in isolated rat kidneys that “hypertensin II” is a potent vasoconstrictor while “hypertensin I” is not, and prepared the enzyme that converts one into the other from horse plasma (PMID 13295487).
Sources: MeSH D000809 and D000808; UniProt P01019; PubMed 17750687 (title only) and 13295487. Read 12 November 2026.
One precursor, eight angiotensins: angiotensin I, II, III, IV, 1-9, 1-7, 1-5 and 1-4
Every angiotensin comes from the first ten amino acids of the mature angiotensinogen chain, positions 25 to 34 of the 476-amino-acid human precursor made by the AGT gene. Each enzyme trims a little more from one end or the other. UniProt maps the six main ones like this:
| Peptide | Positions | Amino acids | Sequence and how it is made |
|---|---|---|---|
| Angiotensinogen | 25-476 | 452 | The precursor protein, made by the liver and released into the blood. Positions 1-24 are a signal sequence removed before release. |
| Angiotensin I | 25-34 | 10 | DRVYIHPFHL. Cut from angiotensinogen by renin. MeSH notes it has limited biological activity of its own. |
| Angiotensin 1-9 | 25-33 | 9 | DRVYIHPFH. Made from angiotensin I by ACE2, which removes the last amino acid. |
| Angiotensin II | 25-32 | 8 | DRVYIHPF. Made from angiotensin I by ACE, which removes the last two amino acids. The main active form. |
| Angiotensin 1-7 | 25-31 | 7 | DRVYIHP. Made from angiotensin II by ACE2 or from angiotensin 1-9 by ACE; acts on the MAS1 receptor. |
| Angiotensin III | 26-32 | 7 | RVYIHPF. Angiotensin II without its first amino acid; UniProt records that it stimulates aldosterone release. |
| Angiotensin IV | 27-32 | 6 | VYIHPF. Angiotensin III without its first amino acid. |
UniProt also lists two shorter pieces, angiotensin 1-5 and 1-4, which ACE makes from angiotensin 1-9, and a variant called angiotensin A, in which white blood cells change the first amino acid of angiotensin II from aspartate to alanine; it binds the AT1 receptor as strongly as angiotensin II and the AT2 receptor more strongly. MeSH notes that the amino acid at position 5 of angiotensin II varies between species. PubChem gives angiotensin I the formula C62H89N17O14 and a molecular weight of 1,296.5 (CID 3081372), angiotensin II C50H71N13O12 and 1,046.2 (CID 172198), and angiotensin 1-7 C41H62N12O11 and 899.0 (CID 123805).
Sources: UniProt P01019; MeSH D000803 and D000804; PubChem CID 3081372, 172198 and 123805. Read 12 November 2026.
The renin-angiotensin system, step by step
MeSH describes the renin-angiotensin system as a blood-pressure regulating system of interacting parts. Read in order, the public records describe this chain:
| Step | Where | What it does |
|---|---|---|
| Renin | The kidney | Cuts angiotensinogen to release angiotensin I. UniProt records that this is renin's only known function. |
| Angiotensin-converting enzyme (ACE) | Highest levels in lung, kidney, heart, gut and prostate | Removes two amino acids from angiotensin I to make angiotensin II. The same enzyme inactivates bradykinin. |
| Angiotensin II at the AT1 receptor | Blood vessels, kidney, adrenal gland and other tissues | Narrows blood vessels, increases salt and water retention by the kidney and stimulates aldosterone release. |
| Aldosterone | Adrenal cortex | A steroid hormone, not a peptide. MeSH records that it further increases salt and water retention in the kidney. |
| ACE2 and angiotensin 1-7 | Heart, kidney, testis, gut and blood vessel lining | Converts angiotensin II to angiotensin 1-7, which acts on the MAS1 receptor and counterbalances angiotensin II. |
UniProt records that renin cuts angiotensinogen in response to low blood pressure, and the Tekturna label adds that the kidney releases renin in response to falls in blood volume and kidney blood flow, and that angiotensin II in turn holds renin release back, closing the loop. With aldosterone included, the chain is often called the renin-angiotensin-aldosterone system, or RAAS. ACE has a second job that matters for medicines: MeSH and UniProt both record that it also breaks down bradykinin, a peptide that widens blood vessels.
Sources: MeSH D012084, D012083 and D007703; UniProt P00797 (renin), P12821 (ACE), Q9BYF1 (ACE2), P01019; Tekturna U.S. label (March 2024), section 12.1. Read 12 November 2026.
The receptors, and the counterweight: AT1, AT2, ACE2 and MAS1
- AT1 receptor (gene AGTR1, 359 amino acids). UniProt records it as the receptor for angiotensin II that regulates blood pressure and sodium retention by the kidney; it couples to Gq proteins, activates phospholipase C and raises calcium inside the cell. MeSH records that activating it causes narrowing of blood vessels and sodium retention, and that it is expressed at high levels in the heart and blood vessels, kidney, endocrine and nervous systems.
- AT2 receptor (gene AGTR2, 363 amino acids). Also a receptor for angiotensin II, but MeSH records that it is expressed at high levels in fetal tissues and that many of its effects, such as widening blood vessels and sodium loss, are the opposite of AT1’s. UniProt notes very high expression in the fetal kidney and intestine.
- ACE2 (805 amino acids). A relative of ACE that removes one amino acid instead of two. UniProt calls it an essential counter-regulatory enzyme of the system: it turns angiotensin II into angiotensin 1-7, and MeSH records that it works 400 times more efficiently on angiotensin II than on angiotensin I. Its discoverers reported in 2000 that it was not inhibited by the ACE inhibitors lisinopril or captopril (PMID 10969042). UniProt also records ACE2 as the cell receptor used by the coronaviruses SARS-CoV and SARS-CoV-2.
- MAS1 receptor (325 amino acids). UniProt records it as the receptor mainly stimulated by angiotensin 1-7, part of what it calls the protective, counter-regulatory arm of the system; angiotensin 1-7 is recorded as having vasodilator and antidiuretic effects (by similarity, that is, inferred from related species).
One more angiotensin has a life outside this system: our dihexa guide covers a synthetic compound built on the angiotensin IV backbone, for which a different target has been proposed.
Sources: UniProt P30556, P50052, Q9BYF1, P04201, P01019; MeSH D044140, D044139 and D000085962; PubMed 10969042 and 10924499 (title only). Read 12 November 2026.
Angiotensin in FDA’s records
Angiotensin II is itself an approved medicine, and three classes of medicines block the system at different steps. The table lists one example per group from Drugs@FDA, searched by active ingredient on 12 November 2026, with the approval year recorded for its original application:
| Product | Application | Approved | What it is and how it relates to angiotensin |
|---|---|---|---|
| Giapreza (angiotensin II) | NDA 209360 | 2017 | Synthetic human angiotensin II, a peptide, given by intravenous infusion. The label is indicated to increase blood pressure in adults with septic or other distributive shock. |
| Capoten (captopril) | NDA 018343 | 1981 | An ACE inhibitor, not a peptide. A U.S. captopril label calls it the first of a new class of antihypertensive agents. Drugs@FDA lists the Capoten brand as discontinued. |
| Cozaar (losartan) | NDA 020386 | 1995 | An angiotensin II receptor blocker acting on the AT1 receptor; the label calls it a non-peptide molecule. Indicated for hypertension and two further uses named on the label. |
| Tekturna (aliskiren) | NDA 021985 | 2007 | A direct renin inhibitor, acting one step earlier than ACE inhibitors. Indicated for hypertension. |
The Giapreza label describes angiotensin II as a naturally occurring peptide hormone that raises blood pressure by narrowing blood vessels and increasing aldosterone release, acting on the AT1 receptor of vascular smooth muscle. The ACE inhibitors trace back to a 1977 paper in Science in which Ondetti, Rubin and Cushman described designing a new class of orally active inhibitors from a model of the enzyme’s active site (PMID 191908). The labels of Cozaar and Tekturna carry a boxed warning that drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. The table is not a list of every product: Drugs@FDA holds dozens of applications for captopril and losartan alone.
Sources: Drugs@FDA via openFDA, searched by active ingredient (original approval dates; data updated 10 November 2026); current U.S. labels for Giapreza (July 2026), Cozaar (January 2026), Tekturna (March 2024) and captopril with hydrochlorothiazide (February 2023); PubChem CID 44093 and 3961; PubMed 191908. Read 12 November 2026. Doses are not reproduced here; the approved medicines that are themselves peptides are on our FDA-approved peptides page.
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Where this sits in the rest of the reference
FAQ
What is angiotensin?
Angiotensin is a family of small peptide hormones that control blood pressure and fluid balance. MeSH describes the angiotensins as oligopeptides important in the regulation of blood pressure and fluid homeostasis via the renin-angiotensin system. All of them are cut from one precursor protein, angiotensinogen, which the liver makes and releases into the blood.
What does angiotensin II do?
UniProt records that angiotensin II acts directly on the smooth muscle of blood vessels as a potent vasoconstrictor, affects how strongly and how fast the heart beats through the sympathetic nervous system, and changes how the kidney absorbs sodium and water by making the adrenal cortex produce aldosterone. It acts through the AT1 and AT2 receptors.
What is the difference between angiotensin I and angiotensin II?
Length and activity. Angiotensin I has ten amino acids (DRVYIHPFHL) and, in MeSH's words, limited biological activity. Angiotensin-converting enzyme removes its last two amino acids to make angiotensin II, eight amino acids long (DRVYIHPF), which MeSH calls a potent but labile vasoconstrictor. PubChem gives angiotensin I a molecular weight of 1,296.5 and angiotensin II one of 1,046.2.
What is the renin-angiotensin system?
MeSH describes it as a blood-pressure regulating system made up of renin, angiotensinogen, angiotensin-converting enzyme, angiotensin I, angiotensin II and angiotensinase. Renin from the kidney cuts angiotensinogen from the liver into angiotensin I; ACE, contained in the lung, converts it into angiotensin II; angiotensin II narrows blood vessels and stimulates aldosterone release from the adrenal cortex, and both increase salt and water retention in the kidney. With aldosterone included it is often called the renin-angiotensin-aldosterone system, or RAAS.
What does ACE do?
Angiotensin-converting enzyme removes two amino acids from the end of several peptide hormones. UniProt records that it converts angiotensin I into angiotensin II and also inactivates bradykinin, a vasodilator, and that it breaks down substance P, neurotensin and enkephalins. ACE inhibitors, the class of medicines that block it, are named after it.
What is ACE2 and how does it relate to angiotensin?
ACE2 is a related enzyme that removes a single amino acid instead of two. UniProt records that it converts angiotensin I to angiotensin 1-9 and angiotensin II to angiotensin 1-7, counterbalancing angiotensin II, and MeSH records that it works 400 times more efficiently on angiotensin II than on angiotensin I. It was described in 2000 (PubMed 10969042), and the authors found it was not inhibited by the ACE inhibitors captopril or lisinopril. UniProt also records ACE2 as the cell receptor for the coronaviruses SARS-CoV and SARS-CoV-2.
What is angiotensin 1-7?
A seven-amino-acid angiotensin (DRVYIHP) made from angiotensin II by ACE2, or from angiotensin 1-9 by ACE. UniProt records it as a ligand for the MAS1 receptor, with vasodilator and antidiuretic effects (statements marked by similarity), and describes MAS1 as part of the protective, counter-regulatory arm of the renin-angiotensin system.
What medicines act on angiotensin?
Three classes block the system at different steps: renin inhibitors such as aliskiren (Tekturna), ACE inhibitors such as captopril, and angiotensin II receptor blockers such as losartan (Cozaar), which act on the AT1 receptor. One medicine is angiotensin II itself: Giapreza, approved in 2017 and labelled to raise blood pressure in adults with septic or other distributive shock. The labels of Cozaar and Tekturna carry a boxed warning that drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. This page reports the labels; decisions about a medicine belong with the prescriber.
Where does the name angiotensin come from?
The name was settled in print in 1958, when Braun-Menéndez and Page published "Suggested revision of nomenclature: angiotensin" in Science (PubMed 17750687; cited by title, as PubMed holds no abstract). Papers from 1956, such as Skeggs and colleagues' work on the converting enzyme, still use the older names hypertensin I and hypertensin II.
Is this medical advice?
No. This page explains what angiotensin is, from public scientific and regulatory sources. It gives no dose, schedule, reference range or recommendation, and it does not interpret blood pressure or test results; anyone taking a medicine named here should follow their own clinician and product label. Peptides sold for research are labelled research use only, not for human use. Medibact supplies USP-grade bacteriostatic water, made in the USA, and is not affiliated with any manufacturer of the products named here.
References: UniProt P01019, P00797, P12821, Q9BYF1, P30556, P50052, P04201; MeSH D000809, D000803, D000804, D000808, D012084, D012083, D007703, D000085962, D044140, D044139, D000806, D057911; PubChem CID 3081372, 172198, 123805, 44093, 3961; PubMed 13295487, 13345963, 17750687, 191908, 10969042, 10924499; Drugs@FDA via openFDA and the current U.S. labels named above. Read 12 November 2026.
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