Bradykinin
Bradykinin, the kinin system mediator
Written by Aaron CuhaReviewed Sep 2026
Also known as: Bradykinin, BK, Kallidin (lysyl-bradykinin) as the related decapeptide
A 9 amino acid inflammatory mediator, not a therapy. It is the reason ACE inhibitors cause cough and angioedema, and human forearm and nerve studies have measured what it does; there is no clinical use for administering it.
Overview
Bradykinin is a 9 amino acid peptide, sequence RPPGFSPFR, released from kininogen by kallikrein enzymes during inflammation and tissue injury. It dilates blood vessels, increases vascular permeability and sensitises pain-carrying nerves. It is destroyed by angiotensin-converting enzyme, which is the single most clinically useful fact about it: ACE inhibitors raise bradykinin as a side effect of lowering angiotensin II, and that is why they cause a dry cough in a minority of users and angioedema in up to about 0.5 percent.
Human evidence about bradykinin comes from measuring rather than treating. Forearm blood flow studies using the antagonist B9340 showed that bradykinin does not maintain resting vessel tone in healthy volunteers, but does contribute to vasodilation in people with heart failure who are taking ACE inhibitors: the antagonist produced vasoconstriction while they were on the drug and not after it was withdrawn. A separate randomised crossover study in 20 healthy men found that blocking the B2 receptor with HOE-140 did not abolish the protection given by remote ischaemic preconditioning, a null result against a popular mechanism. Work on donated human dorsal root ganglion tissue found B2 receptors enriched in pain-sensing neurons and showed that acute bradykinin makes human sensory neurons more excitable, which confirms in human tissue what had been described in rodents.
Bradykinin itself is not a drug and is not approved anywhere for anything. The drug in this family is its antagonist, icatibant, which has its own page.
Mechanism of action
In humans, bradykinin acts at two G protein-coupled receptors: B2, which is present constitutively, and B1, which is induced by inflammation. B2 activation on endothelium releases nitric oxide and prostacyclin, producing vasodilation and increased permeability; on nociceptors it lowers the threshold for firing. Angiotensin-converting enzyme and other peptidases degrade it within seconds, so inhibiting ACE both reduces angiotensin II and raises bradykinin. Human dorsal root ganglion tissue confirms B2 enrichment in the nociceptor population, with B1 expression associated with donor age and a history of chronic pain in that dataset.
Human evidence
There is real human data on bradykinin, and none of it is about giving it as a treatment. People have received infused bradykinin and bradykinin antagonists in controlled physiology experiments, human nerve tissue has been studied directly, and the drug trials that matter are trials of blocking it.
- Forearm blood flow, 8 healthy volunteers and 17 patients with heart failure: bradykinin does not maintain resting arteriolar tone in health, but it does contribute to vasodilation during chronic ACE inhibition, and that contribution disappears when the ACE inhibitor is stopped.
- Randomised crossover, 20 healthy men: B2 receptor blockade did not abolish the protection from remote ischaemic preconditioning, arguing against bradykinin as the mediator of that effect.
- Human dorsal root ganglion tissue from organ donors: B2 receptors are enriched in nociceptors and acute bradykinin increases the excitability of human sensory neurons, confirming a rodent finding in human tissue.
- Clinical pharmacology by subtraction: ACE inhibitor angioedema, which occurs in up to about 0.5 percent of users, resolves faster when the B2 receptor is blocked with icatibant, which is human evidence that bradykinin causes it.
What this does not tell you: These are mechanistic and provocation studies in small numbers of people, several of them in healthy volunteers, and they measure blood flow and nerve excitability rather than any clinical outcome. Nothing here supports administering bradykinin for any purpose, and no trial has tried. The human tissue work is ex vivo, so it describes what neurons do in a dish, not what a person feels.
Reading the research record
Bradykinin appears in peptide catalogues because it is a famous peptide, not because anyone takes it. It belongs here for a different reason: it explains two of the most common adverse effects in all of cardiovascular medicine. ACE breaks bradykinin down, so an ACE inhibitor raises it, and that is the accepted explanation for ACE inhibitor cough and for the angioedema that lands people in emergency departments.
The therapeutic direction the field took was blocking bradykinin rather than supplying it, which is why the drug on this system is an antagonist, icatibant. The one place a bradykinin agonist has been seriously pursued, the blood-brain barrier opening agent lobradimil, is not covered here because no verified current human record was resolved for this batch. Where this page stops is worth stating exactly: there is no published human trial of bradykinin administration as a therapy, which is different from saying it was tried and failed.
The evidence, charted
Fig. 1 · evidence composition
4of 6 citations (67%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 6 distinct years, 2001 to 2024, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Not approved
CA
Not approved
Approved in 1 of 4, prescription route in 0, not approved in 3. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2001
Bradykinin contributes to the vasodilator effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure
Forearm plethysmography studies: in 8 healthy volunteers the antagonist B9340 blocked vasodilation to infused bradykinin without changing resting blood flow. In 17 patients with NYHA class II to IV heart failure on chronic ACE inhibitors, B9340 caused dose-dependent vasoconstriction (p = 0.01), which disappeared after the ACE inhibitor was withdrawn and returned when it was restarted.
Circulation - Human2011
Bradykinin does not mediate remote ischaemic preconditioning or ischaemia-reperfusion injury in vivo in man
Randomised double-blind crossover study in 20 healthy men. The B2 antagonist HOE-140 did not prevent the impairment of endothelium-dependent vasodilation caused by ischaemia-reperfusion, and did not abolish the protection from remote ischaemic preconditioning. A null result against a widely proposed bradykinin mechanism.
Heart - Human2024
Bradykinin receptor expression and bradykinin-mediated sensitization of human sensory neurons
Human dorsal root ganglion tissue from organ donors. B2 and, less so, B1 receptors were found on sensory neurons and satellite glial cells, with B2 enriched in nociceptors. Patch-clamp recording showed acute bradykinin increases human sensory neuron excitability, while prolonged exposure decreases it in a subpopulation. NIH supported.
Pain - Review2018
Pharmacotherapy for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Systematic Review
Systematic review of 5 articles covering 218 cases. States that angioedema occurs in up to 0.5 percent of ACE inhibitor users and is attributed to raised bradykinin. Of the treatments tested, 1 of 2 icatibant studies beat corticosteroids plus antihistamines on speed of improvement; ecallantide and C1 inhibitor replacement showed no significant benefit.
Otolaryngology Head and Neck Surgery - Human2015
A randomized trial of icatibant in ACE-inhibitor-induced angioedema
Phase 2 trial, 27 patients analysed per protocol. Blocking the bradykinin B2 receptor resolved ACE inhibitor angioedema in a median 8.0 hours versus 27.1 hours on prednisolone plus clemastine (p = 0.002). This is the clearest human evidence that bradykinin is the mediator of that reaction. Funded by Shire.
New England Journal of Medicine - Review2004
Bradykinin receptor ligands: therapeutic perspectives
Review of the kinin system and of attempts to drug it, covering B1 and B2 receptor pharmacology and why antagonists rather than agonists became the therapeutic direction.
Nature Reviews Drug Discovery
Frequently asked questions
Can you take bradykinin?
No. There is no bradykinin medicine anywhere. It exists in human studies only as an infused research probe or as the mediator that drugs are designed to block.
Why do ACE inhibitors cause a cough?
Because angiotensin-converting enzyme also destroys bradykinin. Blocking the enzyme raises bradykinin, which sensitises airway nerves. The same mechanism explains ACE inhibitor angioedema, which occurs in up to about 0.5 percent of users and resolves faster when the bradykinin B2 receptor is blocked.
Does bradykinin cause pain?
In human sensory nerve tissue, yes: B2 receptors are concentrated on pain-sensing neurons and acute bradykinin makes them more excitable. That is a tissue finding from organ donors rather than a measurement of pain in a living person.
Is bradykinin involved in COVID-19?
It was proposed as a mechanism and tested by blocking it. A randomised open-label phase 2 trial of icatibant in 73 hospitalised people with COVID-19 pneumonia missed its primary endpoint, so the bradykinin hypothesis in COVID-19 remains unproven rather than established.