Urotensin II
The peptide once called the most potent vasoconstrictor known, and what happened when researchers infused it into people
Urotensin II was found first in fish, then in humans, and in 1999 it was shown to bind an orphan receptor and squeeze monkey arteries about ten times more strongly than endothelin-1. That made it look like a key player in high blood pressure and heart failure. Infused into healthy volunteers, though, it gave mixed results: one forearm study saw blood flow fall, three others saw no effect at all, and in the skin it widened vessels in healthy people but narrowed them in patients with heart failure, hypertension or cirrhosis. Its blood levels are raised in several diseases, but not consistently. Urotensin II itself has never been a treatment.
Used in human trials: 0.1 to 300 pmol/min, stepped up, Continuous infusion, Intra-arterial (brachial artery) (Study: healthy volunteers, forearm blood flow (9 people)) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Urotensin II is a short ring-shaped peptide: eleven amino acids in humans, with two cysteines linked so that six of them form a closed loop. It was named for the urophysis, a small organ at the tail end of the fish spinal cord where it was first isolated decades ago, and the human version was cloned much later. In 1999 a team showed that an orphan receptor called GPR14, found mostly in heart and blood-vessel tissue, was its receptor. In isolated monkey arteries the peptide caused contraction at concentrations about ten times lower than endothelin-1, and given to anaesthetised monkeys it raised vascular resistance sharply and weakened the heart's pumping. On that evidence it was described as the most potent mammalian vasoconstrictor known.
The human studies that followed did not settle the question. Infused into the brachial artery of nine healthy volunteers, it lowered forearm blood flow by about a third at the top rate. A Cambridge group infused it the same way, up to the same top rate, and saw no change in forearm flow or in hand vein diameter; later forearm work in healthy people and in patients with cardiovascular disease again found no effect on the forearm vessels. Given intravenously at rates that raised blood levels about a hundredfold, it changed neither heart rate, blood pressure, cardiac output nor arterial stiffness. Applied to the skin by iontophoresis, a small electric current that carries a drug through the skin, it widened small vessels in healthy people but narrowed them in patients with chronic heart failure, hypertension or cirrhosis, although a study of hypertensive patients who had never taken blood pressure medicine found it widened their skin vessels too.
Measurements in blood have been just as mixed. One study of 126 heart failure patients found urotensin levels raised and nearly as good as NT-proBNP at telling patients from controls; another found no difference between controls and severe heart failure, and no change when patients' circulation improved on treatment. A Chinese case-control study of 197 matched pairs linked higher levels with newly diagnosed high blood pressure, and levels were raised in diabetes. In people on haemodialysis, a higher level went with fewer cardiovascular events, the reverse of what a harmful vasoconstrictor would predict, and patients with acute coronary syndromes had lower levels than people with stable disease. Part of the disagreement is technical: two assays run on the same samples gave different answers, and a related peptide, urotensin-related peptide, shares the ring that antibodies recognise.
Reviews describe a wider role than blood pressure. Urotensin II and its receptor appear in atherosclerotic plaque, the kidney and the brain, and in cell and animal work the peptide promotes inflammation, fibrosis, foam-cell formation and the growth of vascular smooth muscle. That made the receptor an attractive drug target. An oral receptor blocker, palosuran, reached human trials; after an early study suggested less protein in the urine of diabetic patients, a placebo-controlled crossover trial found no effect on albuminuria or blood pressure. Those are trials of a different molecule and are listed under References, not as study cards here.
So urotensin II sits in an unusual place. It is a real human hormone with a known receptor, it can be given to people safely in small research amounts, and it is measured in dozens of disease studies. But the evidence in people never showed the single clear action the animal work promised. Whether it constricts or relaxes a vessel seems to depend on the vessel, the person's health and the state of the endothelium, the inner lining that can release nitric oxide. It is a research tool and a candidate marker, not a medicine, and nothing in the human literature supports taking it.
Mechanism of Action
Urotensin II acts through one receptor, UT, but the same signal can tighten or relax a vessel depending on which cells carry the receptor and how healthy the vessel lining is.
Constriction through smooth muscle
On vascular smooth muscle the UT receptor raises intracellular calcium and contracts the vessel; this is the effect that was so strong in monkey arteries (PMIDs 10499587, 17680191).
Dilation through the endothelium
On endothelial cells the receptor can release nitric oxide and widen the vessel; blocking nitric oxide blunted the skin response in healthy people (PMIDs 17680191, 18568688).
Health decides the balance
Skin vessels widened in healthy people and narrowed in heart failure, hypertension and cirrhosis, suggesting that damaged endothelium tips the response toward constriction (PMIDs 15007012, 16182109, 18938752).
Inflammation and growth in the lab
In cell and animal work it promotes adhesion molecules, foam cells, fibrosis and smooth-muscle growth (PMIDs 19199921, 30601760).
Published Research
These are studies of urotensin II read from their PubMed abstracts: the 1999 receptor paper, the infusion and iontophoresis studies in people, measurements of its blood level in heart, kidney, vascular and metabolic disease, an assay study, and reviews. Trials of drugs that block its receptor are listed under References.
The receptor is found, and monkey arteries clamp down
Human urotensin II bound the orphan receptor GPR14, mostly expressed in heart and vessel tissue, with high affinity and raised calcium in the cell. It contracted isolated monkey arteries about ten times more potently than endothelin-1, and in anaesthetised monkeys it sharply increased peripheral resistance and impaired heart contraction.
Forearm blood flow falls in healthy volunteers
Infused into the brachial artery of nine healthy volunteers at 0.1 to 300 pmol per minute, urotensin II reduced forearm blood flow in a dose-dependent way, starting at 1 pmol per minute and reaching a 31% fall at the top rate. Flow was back to baseline within 30 minutes.
No effect on forearm or hand vein in a second group
In 11 healthy men given brachial infusions from 0.001 to 300 pmol per minute, forearm blood flow did not change, even when nitric oxide and prostaglandins were blocked. Plasma levels rose from about 12 to 307 pmol/L at the top rate without any change in blood pressure, heart rate, cardiac output or the ECG, and local infusion did not narrow hand veins.
Intravenous infusion leaves blood pressure unchanged
Ten healthy men received intravenous urotensin II at 3, 30 and 300 pmol per minute and saline on separate days. Plasma levels rose about a hundredfold, to around 1,460 pmol/L, yet heart rate, mean arterial pressure, cardiac index, augmentation index and pulse wave velocity did not change against placebo. The infusions were well tolerated.
No forearm effect in healthy people or heart patients
Brachial infusion of urotensin II did not change forearm blood flow in ten healthy volunteers or ten patients with cardiovascular disease, nor in six men given a longer infusion. Systolic pressure rose slightly during the ramped infusion, from 133 to 137 mmHg in the healthy group, and heart rate rose by about three beats in the patients.
Skin vessels widen in health, narrow in heart failure
Delivered into forearm skin by iontophoresis and measured with laser Doppler, urotensin II produced a dose-dependent rise in skin blood flow in healthy subjects but a dose-dependent fall in patients with chronic heart failure; the groups differed at the two higher concentrations.
The same split in essential hypertension
Iontophoresed into the forearm skin of 14 normotensive people, urotensin II widened small vessels in a dose-dependent way; in 13 patients with essential hypertension it narrowed them, with significant differences between the groups at the two higher concentrations. Reversing the current's polarity gave no response in either group.
Dilation in untreated hypertension, through nitric oxide
In normotensive volunteers, skin blood flux rose after urotensin II iontophoresis, and blocking nitric oxide synthase with L-NMMA blunted the rise. In 30 patients with essential hypertension who had never taken medication, newly diagnosed or long-standing, skin flux rose by a similar amount to matched normotensive subjects, unlike the constriction an earlier study reported.
Constriction in the skin of people with cirrhosis
Given by iontophoresis to the forearm skin of 14 patients with cirrhosis and 14 matched controls, urotensin II narrowed the small vessels of the patients and widened those of the controls, with the difference significant at the two highest doses. The authors suggest it may matter in portal hypertension.
Healthy skin responds, failing hearts barely do
Iontophoresed at a single concentration, urotensin II raised skin blood flux by 39% in healthy controls but by only 6%, not significant, in heart failure patients. The study also tested an inhibitor of soluble epoxide hydrolase, which shifted the response in opposite directions in the two groups.
No rise in heart failure, by any sampling site
Plasma urotensin II did not differ between 13 controls and patients with moderate or severe heart failure, whether sampled from the pulmonary artery, left ventricle, coronary sinus or an arm vein. A large improvement in circulation with vasodilator therapy did not change it over 24 hours, and its gene expression in heart and vessel tissue was unchanged in end-stage failure.
Separating urotensin II from its look-alike
Because urotensin-related peptide shares the same ring, the authors built an extraction step that separates the two before measuring each by immunoluminometric assay. In 20 patients admitted with acute heart failure and 20 matched controls, both peptides were higher in the patients on admission (urotensin II median 1.29 against 0.50 pmol/L).
Smoking, and two assays that disagree
Among 40 healthy men, a radioimmunoassay found higher plasma urotensin II in smokers than non-smokers, and higher still within 10 minutes of a cigarette. An immunoluminometric assay run on the same samples found consistently low values with no differences between groups, which the authors suggest may explain conflicting reports.
Higher levels in new, untreated hypertension
In 197 newly diagnosed, untreated hypertensive patients and 197 matched normotensive controls, median urotensin II was modestly higher in the patients and correlated with systolic and diastolic pressure. People in the top quarter of levels were about 2.6 times as likely to have hypertension as those in the bottom quarter, independent of nitric oxide metabolites.
Raised in diabetes with normal kidney function
Plasma urotensin II was about 1.7 to 1.8 times higher in diabetic patients with normal creatinine, with or without overt proteinuria, than in healthy subjects, but it did not track fasting glucose, HbA1c or creatinine. Cultured human endothelial cells expressed both the peptide's precursor and its receptor.
In dialysis, higher levels went with fewer heart events
In 191 haemodialysis patients followed for about 3.6 years, plasma urotensin II was roughly twice the level of healthy people, yet it was lower in the 88 patients who had cardiovascular events than in those who did not, and remained an inverse predictor after adjustment, third in rank after age and diabetes.
Lower in acute coronary syndromes
Plasma urotensin II measured with new monoclonal antibodies was lower in 54 patients with acute coronary syndromes than in 51 with stable coronary disease or 29 healthy volunteers, and in both patient groups higher blood pressure went with lower levels.
Is it the new endothelin?
This review traces how urotensin II was hailed as a second endothelin after the monkey artery work, then notes that its effects vary across species and vessel beds, that its maximum effect is smaller than endothelin-1's, and that it can also dilate vessels through the endothelium.
Receptor biology and human findings
The review explains that the UT receptor couples to Gq/11 and raises intracellular calcium, that receptors on smooth muscle constrict while those on endothelium dilate through nitric oxide, and that plasma levels are raised in heart, kidney and liver disease and in diabetes.
A case for a role in atherosclerosis
Drawing on human tissue, cell and mouse work, this review describes urotensin II in endothelial cells and lymphocytes of human plaques, its stimulation of adhesion molecules and foam-cell formation, and the worsening of aortic lesions in mice given chronic infusions; it links a gene variant to hypertension and diabetes in Asian populations.
Dosing Data
Urotensin II is not approved anywhere as a medicine and has no treatment dose. These are the research infusion rates stated in the abstracts of published human studies, each given once under monitoring to measure vessel responses.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Urotensin II is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: intra-arterial (brachial artery), intravenous). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Urotensin II, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Urotensin II stays intact once mixed.
How it is taken
As it was given in human studies: Intra-arterial (brachial artery) (Continuous infusion; Study: healthy volunteers, forearm blood flow (9 people)); Intravenous (Continuous infusion; Study: healthy men, systemic haemodynamics (10 people)).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Study: healthy volunteers, forearm blood flow (9 people): One session; Study: healthy men, forearm and systemic responses (11 people): One session; Study: healthy men, systemic haemodynamics (10 people): One session, with saline on a separate day.
When effects appear: unknown; no source on this page gives a time to effect for Urotensin II. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Intravenous infusions up to 300 pmol per minute were well tolerated, with no clinical adverse effects and no ECG changes (PMID 12492609); Systolic blood pressure rose slightly during ramped brachial infusions, by about 4 mmHg in healthy volunteers (PMID 19843055); Heart rate rose by about three beats per minute in patients with cardiovascular disease during a ramped infusion (PMID 19843055); Forearm blood flow fell by up to 31% during infusion in one study, returning to baseline within 30 minutes (PMID 11786476). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Urotensin II. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Urotensin II has been given to people only in small research studies of a single session; these are the effects their abstracts report”).
Interactions
Unknown: a PubMed search for human interaction studies of Urotensin II (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Urotensin II products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Urotensin II's expected mass, 1,388.6 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine anywhere: no approval and no treatment trial in the sources read). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Urotensin II has been given to people only in small research studies of a single session; these are the effects their abstracts report.
Contraindications & Cautions
There is no product label, so there are no formal contraindications.
Legal Status
Urotensin II is a research peptide; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is urotensin II?
An 11-amino-acid ring-shaped peptide hormone, first found in fish and later in humans, that acts on the UT receptor in heart and blood-vessel tissue.
?Is it really the strongest vasoconstrictor?
In isolated monkey arteries it was about ten times more potent than endothelin-1. In people the picture is mixed: one forearm study saw blood flow fall, several others saw no change, and in the skin it widened vessels in healthy people.
?Has urotensin II been given to people?
Yes, but only in research: short infusions into an artery or vein, measured in picomoles per minute, and skin iontophoresis. These studies looked at vessel responses, not at treating anything.
?Are urotensin II levels a useful blood test?
Not yet. Levels have been reported raised in heart failure, hypertension, diabetes and kidney disease, but other studies disagree, and in dialysis patients higher levels went with fewer heart events. Different assays give different results.
?Are there drugs that block it?
Yes. Palosuran, an oral receptor blocker, reached human trials in diabetic kidney disease but did not lower albuminuria or blood pressure in a placebo-controlled trial. It is a different molecule; its trials are listed under References.
?How long does urotensin II last in the body?
No half-life for it in people was found in the sources read.
References
- [pubmed] Ames RS, et al. "Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14." Nature, 1999;401(6750):282-6. PMID: 10499587.
- [pubmed] Böhm F, et al. "Urotensin II evokes potent vasoconstriction in humans in vivo." Br J Pharmacol, 2002;135(1):25-7. PMID: 11786476.
- [clinical-trial] Wilkinson IB, et al. "High plasma concentrations of human urotensin II do not alter local or systemic hemodynamics in man." Cardiovasc Res, 2002;53(2):341-7. PMID: 11827684.
- [clinical-trial] Affolter JT, et al. "No effect on central or peripheral blood pressure of systemic urotensin II infusion in humans." Br J Clin Pharmacol, 2002;54(6):617-21. PMID: 12492609.
- [pubmed] Cheriyan J, et al. "The effects of urotensin II and urantide on forearm blood flow and systemic haemodynamics in humans." Br J Clin Pharmacol, 2009;68(4):518-23. PMID: 19843055.
- [pubmed] Lim M, et al. "Differential effect of urotensin II on vascular tone in normal subjects and patients with chronic heart failure." Circulation, 2004;109(10):1212-4. PMID: 15007012.
- [pubmed] Sondermeijer B, et al. "Effect of exogenous urotensin-II on vascular tone in skin microcirculation of patients with essential hypertension." Am J Hypertens, 2005;18(9 Pt 1):1195-9. PMID: 16182109.
- [pubmed] Rossi M, et al. "Skin vasodilator effect of exogenous urotensin-II in hypertensives not exposed to antihypertensive medication." Blood Press, 2008;17(1):18-25. PMID: 18568688.
- [pubmed] Kemp W, et al. "Urotensin II in chronic liver disease: in vivo effect on vascular tone." Scand J Gastroenterol, 2008;43(1):103-9. PMID: 18938752.
- [pubmed] Tran L, et al. "Evaluation of the effects of urotensin II and soluble epoxide hydrolase inhibitor on skin microvessel tone in healthy controls and heart failure patients." Cardiovasc Ther, 2012;30(5):295-300. PMID: 21884016.
- [pubmed] Dschietzig T, et al. "Plasma levels and cardiovascular gene expression of urotensin-II in human heart failure." Regul Pept, 2002;110(1):33-8. PMID: 12468107.
- [pubmed] Jani PP, et al. "The differential extraction and immunoluminometric assay of Urotensin II and Urotensin-related peptide in heart failure." Peptides, 2013;40:72-6. PMID: 23270674.
- [pubmed] Gold SJ, et al. "Does cigarette smoking increase plasma urotensin II concentrations?." Eur J Clin Pharmacol, 2007;63(3):253-7. PMID: 17252242.
- [pubmed] Peng H, et al. "Association between human urotensin II and essential hypertension--a 1:1 matched case-control study." PLoS One, 2013;8(12):e81764. PMID: 24339964.
- [pubmed] Totsune K, et al. "Increased plasma urotensin II levels in patients with diabetes mellitus." Clin Sci (Lond), 2003;104(1):1-5. PMID: 12519081.
- [pubmed] Zoccali C, et al. "Urotensin II is an inverse predictor of incident cardiovascular events in end-stage renal disease." Kidney Int, 2006;69(7):1253-8. PMID: 16508659.
- [pubmed] Joyal D, et al. "Urotensin-II levels in acute coronary syndromes." Int J Cardiol, 2006;108(1):31-5. PMID: 16516696.
- [review] Maguire JJ, et al. "Is urotensin-II the new endothelin?." Br J Pharmacol, 2002;137(5):579-88. PMID: 12381671.
- [review] McDonald J, et al. "Role of urotensin II and its receptor in health and disease." J Anesth, 2007;21(3):378-89. PMID: 17680191.
- [review] Watanabe T, et al. "Human urotensin II promotes hypertension and atherosclerotic cardiovascular diseases." Curr Med Chem, 2009;16(5):550-63. PMID: 19199921.
- [review] Sun SL, et al. "Urotensin II: an inflammatory cytokine." J Endocrinol, 2019;240(3):R107-R117. PMID: 30601760.
- [pubmed] Ng LL, et al. "Plasma urotensin in human systolic heart failure." Circulation, 2002;106(23):2877-80. PMID: 12460864.
- [pubmed] Vogt L, et al. "Effect of the urotensin receptor antagonist palosuran in hypertensive patients with type 2 diabetic nephropathy." Hypertension, 2010;55(5):1206-9. PMID: 20231521.
- [pubmed] Sidharta PN, et al. "Pharmacodynamics and pharmacokinetics of the urotensin II receptor antagonist palosuran in macroalbuminuric, diabetic patients." Clin Pharmacol Ther, 2006;80(3):246-56. PMID: 16952491.
- [pubmed] Sidharta PN, et al. "Pharmacokinetics and pharmacodynamics of the urotensin-II receptor antagonist palosuran in healthy male subjects." J Clin Pharmacol, 2009;49(10):1168-75. PMID: 19625629.
- [other] UniProt O95399 (UTS2_HUMAN), peptide residues 114-124, disulfide 118-123, urotensin-2; read October 28, 2026. https://www.uniprot.org/uniprotkb/O95399/entry
- [other] PubChem CID 46225600, Urotensin II: formula C64H85N13O18S2, molecular weight 1388.6. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/46225600
Sources & Citations
Every study on this page was read from its PubMed record on October 28, 2026. Status comes from Drugs@FDA (openFDA) and the EMA medicines list, read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.