Urocortin 2
A corticotropin-releasing factor relative that acts on the CRF2 receptor, infused into healthy men and heart failure patients in short research studies
Urocortin 2 belongs to the corticotropin-releasing factor family but, unlike its parent hormone, binds only the type 2 CRF receptor, which is plentiful in the heart and blood vessels. Short intravenous infusions in healthy men and in people with heart failure raised cardiac output and lowered blood pressure and vascular resistance, and a 53-patient randomised trial tried it in acute heart failure. No product has been approved and no study has run longer than a day.
Used in human trials: 25 µg or 100 µg, Single infusion, Intravenous (Study: chronic heart failure, 8 men (placebo-controlled dose escala...) 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?
Urocortin 2 was found in 2001 by two groups reading the newly published human genome for sequences that resembled corticotropin-releasing factor (CRF), the hormone that starts the stress response. One group cloned the mouse version and named it urocortin II; the other described the human peptides as stresscopin and stresscopin-related peptide. Both found the same thing about its target: it binds the type 2 CRF receptor and leaves the type 1 receptor, the one that drives ACTH and cortisol release, essentially alone.
That selectivity is why cardiologists became interested. The type 2 receptor is common in the heart and in the walls of blood vessels, and in animals urocortin 2 made the heart contract harder while relaxing the arteries. In sheep with heart failure, a four-day infusion kept cardiac output up and filling pressure down for the whole period and dampened the hormone systems that make the body hold salt and water. In isolated coronary arteries taken from heart transplant recipients, the peptide relaxed the vessel wall by a route that did not need the inner lining of the vessel.
Human studies followed in 2007. Eight healthy men received placebo, 25 µg and 100 µg infusions over an hour on separate days; cardiac output, heart rate and ejection fraction rose with the dose and vascular resistance fell, and the higher dose also switched on renin, angiotensin II and noradrenaline. The same design in eight men with stable heart failure gave the same direction of change in cardiac output, ejection fraction and resistance, without the hormone rise. A 2016 study compared it with urocortin 3 in the forearm and the whole circulation and found both dilate arteries in patients and healthy people alike.
The largest test is the UNICORN trial: 53 people admitted with acute decompensated heart failure were randomised to a four-hour infusion of urocortin 2 or placebo on top of usual treatment. Cardiac output rose by about 2 litres a minute while it did not change with placebo, systolic blood pressure fell, and BNP fell over the next day; urine output and creatinine clearance dipped during the infusion and then recovered. A 2021 meta-analysis pooling the short infusion studies in heart failure confirmed the fall in blood pressure and a small rise in heart rate.
The body's own urocortin 2 can be measured in blood, and studies have found it raised in hypertension, related to fluid overload in acute heart failure, and, as its N-terminal prohormone fragment, inversely related to death over two years in chronic heart failure. These are associations, and the assays differ between studies.
Urocortin 2 is not approved anywhere. Its human use has been limited to single infusions lasting one to four hours under monitoring. Animal work has moved on to delivering its gene with a viral vector, which raised heart function in mice for months, but that is still a laboratory approach.
Mechanism of Action
Urocortin 2 acts on the type 2 corticotropin-releasing factor receptor, which sits on heart muscle and blood vessels, so in people it works mainly as a vasodilator that also lets the heart pump more, rather than as a stress hormone.
Heart output
Infusions raised cardiac output and ejection fraction in healthy men and in heart failure, and in sheep with heart failure contractility stayed higher across four days.
Vessel relaxation
It lowered systemic vascular resistance in people, dilated forearm arteries, and relaxed human coronary artery rings through adenylyl cyclase and protein kinase A, without needing the endothelium.
Salt and water hormones
In sheep it suppressed renin, aldosterone, vasopressin and endothelin over days; in people a brief renin rise followed the drop in blood pressure.
Receptor selectivity
It binds CRF-R2 and not CRF-R1, so unlike CRF it did not raise stress hormones in rodents and did not cause the malaise seen with CRF1 agonists.
Published Research
These are studies of urocortin 2 itself, read from their PubMed abstracts: infusions in healthy volunteers and in chronic and acute heart failure, measurements of the body's own urocortin 2 in patients, work on human tissue and cells, animal studies including gene transfer of urocortin 2, and reviews. Studies of other urocortins appear only where urocortin 2 was tested alongside them.
Higher cardiac output in heart failure
In a single-blind, placebo-controlled dose-escalation study, eight men with heart failure (ejection fraction under 40%) received placebo, then 25 µg and 100 µg of urocortin 2 over an hour. Peak cardiac output rose by 1.0 and 2.0 L/min against 0.3 with placebo, ejection fraction rose by about 6 and 14 points, and blood pressure, vascular resistance and cardiac work fell. Vasoconstrictor hormones did not change; urine volume fell slightly.
Dose-related effects in healthy men
Eight healthy men each had placebo, 25 µg and 100 µg infusions over an hour on separate occasions weeks apart. Cardiac output rose by 2.1 and 5.0 L/min, heart rate by about 9 and 18 beats a minute, and ejection fraction by about 7 and 14 points, while vascular resistance fell. Only the 100 µg dose raised renin, angiotensin II and noradrenaline, and urine volume and sodium output dipped a little.
UNICORN: a 4-hour infusion in acute heart failure
Fifty-three patients admitted with acute decompensated heart failure were randomised to urocortin 2 at 5 ng/kg/min or placebo for four hours on top of usual care. Cardiac output rose by 2.1 L/min against no change with placebo, peripheral resistance fell by about half and systolic pressure dropped more, without a significant rise in heart rate. Urine output and creatinine clearance fell during the infusion but recovered above baseline within eight hours, and BNP fell over 24 hours only with urocortin 2.
Compared with urocortin 3 in health and heart failure
Forearm blood flow studies in eight patients with heart failure and eight matched healthy people showed that intra-arterial urocortin 2 dilated the arteries in a dose-dependent way, as much in patients as in controls. Given intravenously, it lowered blood pressure and vascular resistance like urocortin 3 did; its rise in cardiac index reached significance in the heart failure group and its rise in heart rate in the healthy group.
Sympathetic nerve traffic rose as pressure fell
A 60-minute infusion of 25 µg in eight healthy men lowered mean arterial pressure to 84 against 95 mmHg with placebo, raised heart rate and cardiac output and cut peripheral resistance by about a quarter. Recorded muscle sympathetic nerve bursts increased, the opposite of the fall in cardiac sympathetic activity seen in sheep, which the authors put down to the baroreflex responding to vasodilation. Four men with stable heart failure responded in the same way.
An assay for its prohormone fragment in heart failure
A new sandwich ELISA measured the N-terminal fragment of pro-urocortin 2 in 160 people without heart failure and 255 with it. Median levels were slightly higher in heart failure, about 119 against 112 ng/L, with no difference between reduced and preserved ejection fraction. Within heart failure, higher levels were independently linked to lower two-year mortality, an unexpected direction the authors said needs confirming.
Blood levels tracked lower ejection fraction
A newly developed urocortin 2 assay in 52 patients with heart failure found that blood urocortin 2 rose as ejection fraction fell. It did not correlate with BNP, and it was higher in patients with cardiomyopathy than in other heart failure patients.
A marker of fluid overload in acute heart failure
In admission blood from 80 patients with acute heart failure, median serum urocortin 2 was 2.3 ng/mL. Higher levels went with leg swelling, an enlarged liver, a higher sodium-retention score, dilated right heart chambers and higher pulmonary artery pressure, but not with left heart structure or function, age or sex.
Levels differ with the degree of systolic dysfunction
Among 86 people who had coronary angiography, serum urocortin 2 was lower in those with moderate to severe systolic dysfunction and higher in those with mild to moderate dysfunction than in people with normal pumping. It did not differ with diastolic dysfunction or with coronary artery disease alone.
Higher in hypertension
Serum urocortin 2 was markedly higher in 86 people with hypertension than in 53 without it (median 5.17 against 0.79 ng/mL), correlated modestly with left ventricular mass and body mass index, and remained an independent predictor of hypertension after adjustment for other factors.
Levels differed with blood pressure drugs
In 65 people with hypertension on at least three drugs, serum urocortin 2 was about twice as high in those taking an ACE inhibitor as in those taking an angiotensin receptor blocker (10.9 against 5.6 ng/mL). Beta-blockers, calcium channel blockers and diuretics made no difference.
Arterial stiffness in children with obesity
In a case-control study of 154 children aged 10 to 18, urocortin 2 tended to be lower in the 95 with obesity, though not significantly. Within that group, lower urocortin 2 went with higher body mass index, wider pulse pressure and stiffer arteries by estimated pulse wave velocity.
Relaxes coronary arteries from failing hearts
Coronary artery rings were taken from 17 transplant recipients with ischaemic heart failure. Urocortin 2 at 5 to 20 nmol/L relaxed pre-contracted rings in a dose-dependent way that did not depend on the endothelium; blocking adenylyl cyclase or protein kinase A prevented the relaxation.
Human cells release a prohormone, not the short peptide
Cell lines engineered to make human urocortin 2, and melanoma cells that make it naturally, secreted an 88-residue glycosylated prohormone and did not cut it down further or amidate it, unlike mouse cells, which released a 39-residue amidated peptide. The unprocessed human prohormone still activated the CRF2 receptor.
Discovery: a CRF relative that binds only CRF-R2
Searching the human genome for CRF-like sequences led to a mouse gene copy encoding a predicted 38-residue peptide. It bound the type 2 CRF receptor selectively, was expressed in stress-related brain areas, and given into the brain of rodents reduced night-time feeding without raising general activity as CRF does.
The human peptides named stresscopin-related
The same year another group identified human stresscopin and stresscopin-related peptide as selective ligands of the type 2 CRH receptor. Their genes were active in many peripheral tissues and the brain, and treatment suppressed food intake, slowed stomach emptying and reduced heat-induced swelling in animals.
Four days of infusion in sheep with heart failure
Sheep with pacing-induced heart failure received urocortin 2 at 0.75 µg/kg per hour or saline for four days. Contractility and cardiac output rose within 30 minutes and stayed up, left atrial pressure fell from 28 to 12 mmHg, renin, aldosterone, vasopressin, endothelin and natriuretic peptides fell, and sodium excretion quadrupled. Food intake dropped for a time and cortisol rose briefly on day one.
Kidney and heart protection compared with dobutamine
In sheep with acute decompensated heart failure, two days of urocortin 2 matched dobutamine's gains in contractility and output but lowered filling pressures more, caused a natriuresis that dobutamine did not, and reduced collagen and markers of inflammation, injury and hypertrophy in heart and kidney tissue.
Less pulmonary hypertension in rats
Urocortin 2 and its receptor were increased in the right ventricle of patients and rats with pulmonary arterial hypertension. In rats with monocrotaline-induced disease, human urocortin 2 given for ten days reduced pulmonary pressure and right ventricular remodelling and improved exercise capacity; it also limited right ventricular hypertrophy after pulmonary artery banding.
Suppresses feeding without malaise
In rats, injected urocortin 2 reduced how often they ate through the CRF2 receptor and, unlike CRF1-acting peptides, caused no taste aversion, diarrhoea or rise in corticosterone. It did not reduce feeding in mice lacking CRF2.
Gene transfer improved failing mouse hearts
Mice with heart failure after a heart attack were given one intravenous injection of a viral vector carrying the urocortin 2 gene. Five weeks later ejection fraction was higher than in untreated mice, the rates of pressure rise and fall in the left ventricle were 2.0 and 1.6 times higher, and heart cells handled calcium better.
Its case in cardiovascular disease
A review summarises urocortin 2's effects through the CRF2 receptor: coronary vasodilation, stronger contraction and output, and protection against ischaemia-reperfusion injury in animals, with improved performance and survival in animal heart failure and early benefit in patients with stable chronic heart failure.
Dosing Data
Urocortin 2 is not approved anywhere as a medicine. These are the amounts given in published human studies, as their abstracts state them; each was a single infusion lasting one to four hours under monitoring.
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 Urocortin 2 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, 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 Urocortin 2, 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 Urocortin 2 stays intact once mixed.
How it is taken
As it was given in human studies: Intravenous (Single infusion; Study: chronic heart failure, 8 men (placebo-controlled dose escalation)); Intra-arterial (Stepped infusion into the brachial artery; Study: forearm blood flow, heart failure and healthy volunteers).
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: chronic heart failure, 8 men (placebo-controlled dose escalation): 1 hour; Study: healthy men, 8 (placebo-controlled dose escalation): 1 hour; Study: acute decompensated heart failure, 53 patients (randomised, placebo-controlled): 4 hours.
When effects appear: unknown; no source on this page gives a time to effect for Urocortin 2. 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: Fall in blood pressure, the main effect at every dose (PMIDs 17720993, 24621976); Faster heart rate, larger in healthy men than in heart failure (PMIDs 17258092, 17720993); Rise in renin, angiotensin II and noradrenaline at 100 µg in healthy men (PMID 17258092); Lower urine output and creatinine clearance during infusion, recovering afterwards (PMIDs 17720993, 24621976); More muscle sympathetic nerve activity as blood pressure fell (PMID 26173485). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Urocortin 2. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the short infusion studies above; none ran longer than four hours”).
Interactions
Unknown: a PubMed search for human interaction studies of Urocortin 2 (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 Urocortin 2 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 Urocortin 2's expected mass, 4,450.3 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not approved anywhere). 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
From the short infusion studies above; none ran longer than four hours.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Urocortin 2 is a research peptide; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is urocortin 2?
A peptide of the corticotropin-releasing factor family, found in 2001, that binds only the type 2 CRF receptor. That receptor is common in the heart and blood vessels, so its main effects in people are on the circulation.
?Has urocortin 2 been tested in people?
Yes, in short intravenous infusions: in healthy men, in men with stable heart failure, and in a 53-patient randomised trial in acute heart failure. Each raised cardiac output and lowered blood pressure and vascular resistance.
?Is it a stress hormone like CRF?
No. CRF drives the stress hormone cascade through the type 1 receptor. Urocortin 2 does not act on that receptor, and in rats it did not raise corticosterone.
?Is urocortin 2 approved for heart failure?
No. Drugs@FDA and the EMA list hold no record for it, and no study has given it for more than four hours.
?Can it be measured in blood?
Yes, with research assays. Studies found it higher in hypertension, related to fluid overload in acute heart failure, and, as its prohormone fragment, linked to survival in chronic heart failure, but the assays differ between studies.
?What is urocortin 2 gene transfer?
An approach tested in mice, where a viral vector carrying the urocortin 2 gene is injected once so the body keeps making the peptide. It improved heart function in failing mouse hearts for weeks to months; it has not reached patients in the studies read.
References
- [clinical-trial] Davis ME, et al. "Urocortin 2 infusion in human heart failure." Eur Heart J, 2007;28(21):2589-97. PMID: 17720993.
- [clinical-trial] Davis ME, et al. "Urocortin 2 infusion in healthy humans: hemodynamic, neurohormonal, and renal responses." J Am Coll Cardiol, 2007;49(4):461-71. PMID: 17258092.
- [clinical-trial] Chan WY, et al. "Urocortin-2 infusion in acute decompensated heart failure: findings from the UNICORN study (urocortin-2 in the treatment of acute heart failure as an adjunct over conventional therapy)." JACC Heart Fail, 2013;1(5):433-41. PMID: 24621976.
- [clinical-trial] Stirrat CG, et al. "Cardiovascular effects of urocortin 2 and urocortin 3 in patients with chronic heart failure." Br J Clin Pharmacol, 2016;82(4):974-82. PMID: 27275843.
- [pubmed] Chan WYW, et al. "Human muscle sympathetic nerve responses to urocortin-2 in health and stable heart failure." Clin Exp Pharmacol Physiol, 2015;42(9):888-895. PMID: 26173485.
- [pubmed] Liew OW, et al. "High-Sensitivity Sandwich ELISA for Plasma NT-proUcn2: Plasma Concentrations and Relationship to Mortality in Heart Failure." Clin Chem, 2016;62(6):856-65. PMID: 27127183.
- [pubmed] Inukai K, et al. "Urocortin2 measurement for heart failure assessment." Sci Rep, 2025;15(1):14381. PMID: 40275076.
- [review] Pintalhao M, et al. "Urocortin-2 in Acute Heart Failure: Role as a Marker of Volume Overload and Pulmonary Hypertension." Curr Probl Cardiol, 2022;47(4):100860. PMID: 33994037.
- [pubmed] Topal E, et al. "Relationship of urocortin-2 with systolic and diastolic functions and coronary artery disease: an observational study." Anadolu Kardiyol Derg, 2012;12(2):115-20. PMID: 22281790.
- [pubmed] Aslan G, et al. "Evaluation of Serum Urocortin 2 Levels in Patients with Hypertension." High Blood Press Cardiovasc Prev, 2020;27(1):35-42. PMID: 31925709.
- [pubmed] Walczewska J, et al. "Urocortin 2 in patients with hypertension treated with angiotensin converting enzyme inhibitors or angiotensin receptor blockers." J Physiol Pharmacol, 2019;70(2). PMID: 31443094.
- [pubmed] Kırlı U, et al. "The Role of Urocortin 2 in Arterial Stiffness and Hypertension in Children with Obesity." Children (Basel), 2026;13(10). PMID: 42940746.
- [review] Kovács DK, et al. "Assessment of clinical data on urocortins and their therapeutic potential in cardiovascular diseases: A systematic review and meta-analysis." Clin Transl Sci, 2021;14(6):2461-2473. PMID: 34378854.
- [pubmed] Smani T, et al. "Urocortin-2 induces vasorelaxation of coronary arteries isolated from patients with heart failure." Clin Exp Pharmacol Physiol, 2011;38(1):71-6. PMID: 21105894.
- [pubmed] Vaughan JM, et al. "Posttranslational processing of human and mouse urocortin 2: characterization and bioactivity of gene products." Endocrinology, 2013;154(4):1553-64. PMID: 23493376.
- [pubmed] Reyes TM, et al. "Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors." Proc Natl Acad Sci U S A, 2001;98(5):2843-8. PMID: 11226328.
- [pubmed] Hsu SY, et al. "Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor." Nat Med, 2001;7(5):605-11. PMID: 11329063.
- [pubmed] Rademaker MT, et al. "Prolonged urocortin 2 administration in experimental heart failure: sustained hemodynamic, endocrine, and renal effects." Hypertension, 2011;57(6):1136-44. PMID: 21536988.
- [pubmed] Rademaker MT, et al. "Urocortin 2 protects heart and kidney structure and function in an ovine model of acute decompensated heart failure: Comparison with dobutamine." Int J Cardiol, 2015;197:56-65. PMID: 26113475.
- [pubmed] Adão R, et al. "Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension." Cardiovasc Res, 2018;114(8):1165-1177. PMID: 29584808.
- [pubmed] Fekete EM, et al. "Systemic urocortin 2, but not urocortin 1 or stressin 1-A, suppresses feeding via CRF2 receptors without malaise and stress." Br J Pharmacol, 2011;164(8):1959-75. PMID: 21627635.
- [pubmed] Lai NC, et al. "Intravenous AAV8 Encoding Urocortin-2 Increases Function of the Failing Heart in Mice." Hum Gene Ther, 2015;26(6):347-56. PMID: 25760560.
- [review] Adão R, et al. "Urocortin 2 in cardiovascular health and disease." Drug Discov Today, 2015;20(7):906-14. PMID: 25748088.
- [other] UniProt Q96RP3 (UCN2_HUMAN), chain residues 72-112, urocortin-2; read October 28, 2026. https://www.uniprot.org/uniprotkb/Q96RP3/entry
- [other] PubChem CID 56843276, Urocortin-2: formula C194H339N63O54S, molecular weight 4450. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/56843276
Sources & Citations
Every study on this page was read from its PubMed record on October 28 or 29, 2026. Regulatory status comes from Drugs@FDA (openFDA) and the EMA medicines list. 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.