Bradykinin
A nine-amino-acid peptide that widens vessels and makes them leak, studied by challenge and blocked by icatibant
Bradykinin is a nine-amino-acid peptide cut from blood proteins by kallikrein enzymes. Acting on B2 receptors, it widens blood vessels, makes them leak, and drives inflammation and pain. Injected into skin it raises wheals; inhaled, it narrows the airways of people with asthma. It is never a treatment, but blocking its receptor with icatibant treats hereditary angioedema attacks.
What is it?
Kinins are produced when kallikrein enzymes act on blood proteins. They are local-acting peptides with two receptors, B1 and B2, and they regulate circulation and kidney function and promote inflammation and pain when tissue is injured. Bradykinin and kallidin act on B2; a fragment, des-Arg9-bradykinin, acts on B1.
Challenge studies show what it does in people. Infused into the arm before a period of ischaemia, it protected the artery lining in healthy men, and it accounts for part of the blood-pressure fall in heart failure patients taking sacubitril/valsartan long term. Injected into the skin of 16 volunteers, bradykinin and kallidin produced dose-dependent wheal and flare responses in everyone, while the B1 fragment did so only at the highest dose. Inhaled, bradykinin narrowed the airways of all ten people with asthma tested, more potently than histamine, but affected only one of six healthy people; the effect peaked within 5 minutes and passed within 45.
Blocking it is where the medicine is. Icatibant, a B2 antagonist, is approved as Firazyr for acute attacks of hereditary angioedema in adults. In a small crossover study in dialysis patients prone to blood pressure falls, icatibant prevented the drop that placebo allowed. Newer agents work further upstream: a review of garadacimab, a monthly injection, cites a 91.5% reduction in attacks in its phase 3 trial.
Measuring bradykinin has become practical through a trick: chilling whole blood lets it accumulate, and levels were more than 100-fold higher in hereditary angioedema than in healthy volunteers, with about 91% sensitivity. The same approach detects bradykinin-mediated angioedema when C1-inhibitor is normal, and levels fall on prophylaxis. It is also the usual mechanism behind angioedema reported with clot-busting drugs.
Elsewhere, blocking it keeps disappointing. The B1 antagonist fulmetibant did nothing for diabetic nerve pain in a randomised crossover trial, and icatibant's effect in COVID-19 was limited to a weakening of the link between inflammation and outcomes in a post hoc analysis. Bradykinin itself is never given as a treatment.
Mechanism of Action
Bradykinin is a kinin released when kallikrein acts on blood proteins; it acts on the B2 receptor, while its fragment des-Arg9-bradykinin acts on B1.
Vascular leak
B2 activation causes the swelling of bradykinin-mediated angioedema, which icatibant blocks.
Airways
Inhaled, it constricted asthmatic airways at concentrations far below those needed in healthy people.
Blood pressure
It contributes modestly to the blood-pressure fall on sacubitril/valsartan and protected the artery lining before ischaemia.
Published Research
These are the studies that describe bradykinin in people, read from their PubMed abstracts: two challenge studies, a blockade trial and a review.
In the skin
In eight atopic and eight non-atopic volunteers, intradermal bradykinin and kallidin produced dose-dependent wheal and flare in everyone; the B1 agonist des-Arg9-bradykinin worked only at the top 50 nmol dose.
In the airways
Inhaled bradykinin narrowed the airways of all ten asthmatics, at lower concentrations than histamine, but affected one of six healthy people. Effects peaked within 3 to 5 minutes and resolved over 30 to 45.
Blocking it during dialysis
In a crossover analysis of 11 dialysis patients, icatibant prevented the blood pressure fall seen on placebo in the seven prone to it (nadir 125.6 against 114.3 mmHg) and had no effect in the others.
Protecting the artery lining
In 16 healthy young men, bradykinin infused into the brachial artery before 20 minutes of forearm ischaemia preserved flow-mediated dilation of the radial artery after reperfusion (7% against 8% at baseline), which fell from 8% to 3% after saline.
Part of sacubitril/valsartan's effect
In a crossover trial in heart failure, blocking bradykinin's B2 receptor with icatibant did not change the first-dose fall in blood pressure from sacubitril/valsartan, but after 8 weeks it blunted the fall (9 against 12 mm Hg), a modest bradykinin contribution.
A cold-activation blood test
Incubating whole blood in the cold raised total bradykinin more than 100-fold in people with hereditary angioedema against healthy volunteers (324.3 against 2.3 ng/mL), giving 90.9% sensitivity and 97.1% specificity and tracking kallikrein activity.
A functional marker when C1-inhibitor is normal
Raised bradykinin after ex vivo activation was found in 90.3% of hereditary angioedema patients and 57.4% of suspected bradykinin-mediated angioedema with normal C1-inhibitor; it rose during attacks and fell on kallikrein-inhibitor prophylaxis.
A B1 blocker fails in nerve pain
In a randomised crossover trial in diabetic neuropathic pain, the bradykinin B1 receptor antagonist fulmetibant 450 mg daily gave no benefit over placebo at 4 weeks, despite preclinical promise.
Angioedema after clot-busting drugs
Among 151 reported cases of angioedema with tissue plasminogen activators, 92% of those that could be classified were bradykinin-mediated, and icatibant or C1 inhibitor was first-line in 68% of specified cases.
Icatibant in COVID-19
A post hoc analysis of the ICAT-COVID trial found that icatibant exposure weakened the link between inflammatory markers and clinical events, an effect that faded over time.
Levels in severe COVID-19
During acute COVID-19, plasma bradykinin and substance P were lower than in healthy controls while the B1 fragment DABK was higher; levels differed again at 2.5-year follow-up.
How fast blood breaks it down
In healthy volunteers, serum capacity to degrade labelled bradykinin was higher in men than women, with no relation to ethnicity, BMI or fasting.
Drugs at its receptors
Kinins act through two G-protein-coupled receptors, regulate circulation and kidney function, and promote inflammation and pain, making receptor blockers candidate treatments, including painkillers without tolerance.
Prophylaxis upstream of bradykinin
A review of garadacimab, a monthly 200 mg injection acting upstream in the bradykinin pathway, cites a phase 3 trial reporting a 91.5% reduction in hereditary angioedema attacks with about 77% of patients attack-free.
Aortic dissection in mice
Bradykinin was raised in patients and mice with type A aortic dissection, and icatibant reduced its incidence and mortality in mice independently of blood pressure by restoring endothelial nitric oxide.
Dosing Data
Bradykinin is not a treatment. Research studies infuse, inhale or inject tiny amounts as a challenge.
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.
Side Effects & Contraindications
Reported Side Effects
From the challenge studies; it is never given as treatment.
Contraindications & Cautions
Not a treatment.
Legal Status
Bradykinin is not a medicine; a drug that blocks it is.
Frequently Asked Questions
?What is bradykinin?
A nine-amino-acid peptide that widens and loosens blood vessels and drives inflammation and pain through B2 receptors.
?Does it cause asthma attacks?
Inhaled, it narrowed the airways of all ten asthmatics tested and one of six healthy people.
?Is there a drug that blocks it?
Yes. Icatibant, sold as Firazyr, blocks its B2 receptor and treats acute hereditary angioedema attacks.
?Is it ever given as treatment?
No. It is used in research only, as a challenge agent.
?Can bradykinin be measured to diagnose angioedema?
A cold-activation blood test raised bradykinin more than 100-fold in hereditary angioedema against healthy volunteers, with about 91% sensitivity, and the same approach detects bradykinin-mediated angioedema when C1-inhibitor is normal.
?Have bradykinin blockers worked for pain?
Not so far. The B1 receptor antagonist fulmetibant gave no benefit over placebo in diabetic neuropathic pain in a randomised crossover trial.
References
- [pubmed] Polosa R, et al. "Skin responses to bradykinin, kallidin, and [desArg9]-bradykinin in nonatopic and atopic volunteers." J Allergy Clin Immunol, 1993;92(5):683-9. PMID: 8227859.
- [pubmed] Polosa R, et al. "Comparative airway response to inhaled bradykinin, kallidin, and [des-Arg9]bradykinin in normal and asthmatic subjects." Am Rev Respir Dis, 1990;142(6 Pt 1):1367-71. PMID: 2174657.
- [pubmed] Gamboa JL, et al. "Bradykinin B(2) receptor blockade and intradialytic hypotension." BMC Nephrol, 2023;24(1):134. PMID: 37170244.
- [pubmed] Marceau F, et al. "Bradykinin receptor ligands: therapeutic perspectives." Nat Rev Drug Discov, 2004;3(10):845-52. PMID: 15459675.
- [pubmed] Garvin MR, et al. "A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm." Elife, 2020;9. PMID: 32633718.
- [fda-pi] FIRAZYR (icatibant) injection Prescribing Information, sections 1 (DailyMed version 19, effective July 7, 2025; read September 30, 2026).
- [other] US FDA, Drugs@FDA (openFDA): no application for bradykinin. Read September 30, 2026.
- [clinical-trial] Liuba P, et al. "Bradykinin preconditions postischemic arterial endothelial function in humans." J Card Surg, 2005;20(5):420-4. PMID: 16153271.
- [clinical-trial] Gupta DK, et al. "Modest Contribution of Bradykinin to Blood Pressure Reduction by Sacubitril/Valsartan in Chronic Heart Failure." Circ Heart Fail, 2026;19(6):e014117. PMID: 42028604.
- [pubmed] Chen J, et al. "Bradykinin measurement by liquid chromatography tandem mass spectrometry in subjects with hereditary angioedema enhanced by cold activation." J Allergy Clin Immunol Glob, 2025;4(3):100505. PMID: 40677613.
- [pubmed] Chen J, et al. "Ex vivo bradykinin as a functional biomarker for angioedema with normal C1-inhibitor." J Allergy Clin Immunol Glob, 2026;5(4):100735. PMID: 42328484.
- [pubmed] Stemper B, et al. "The bradykinin-1 receptor antagonist fulmetibant in patients with diabetic neuropathic pain: the randomized, crossover, placebo-controlled, double-blind, phase 2a BRADiNP study." Pain, 2025;166(10):2421-2429. PMID: 40334047.
- [pubmed] Maurier A, et al. "Angioedema reported with tissue plasminogen activators: A need to communicate on bradykinin- and histamine-mediated mechanisms." Therapie, 2026. PMID: 41741276.
- [pubmed] Chandani HK, et al. "Garadacimab and the future of hereditary angioedema prophylaxis: a step upstream in the bradykinin pathway." Ann Med Surg (Lond), 2026;88(7):3924-3927. PMID: 42433832.
- [pubmed] Malchair P, et al. "Pathophysiology of COVID-19: A Post Hoc Analysis of the ICAT-COVID Clinical Trial of the Bradykinin Antagonist Icatibant." Pathogens, 2025;14(6). PMID: 40559541.
- [pubmed] Heinicke U, et al. "Systemic role of orexin A, substance P, bradykinin, and DABK in severe COVID-19 and 2.5-yr follow-ups: an observational study." BJA Open, 2025;14:100415. PMID: 40529720.
- [pubmed] Bayer M, et al. "The Biological Variation in Serum ACE and CPN/CPB2 Activity in Healthy Individuals as Measured by the Degradation of Dabsylated Bradykinin-Reference Data and the Importance of Pre-Analytical Standardization." Proteomes, 2025;13(3). PMID: 40981200.
- [pubmed] Zhao S, et al. "Overactivated bradykinin-B2 receptor promotes type a aortic dissection by inducing endothelial dysfunction: Therapeutic effect of icatibant." Life Sci, 2026;402:124572. PMID: 42413717.
Sources & Citations
Studies were read from their PubMed abstracts. Read October 7, 2026.
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