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Bradykinin

An endogenous 9-amino-acid vasoactive peptide generated by kallikrein cleavage of kininogen; the primary effector of the kinin-kallikrein system, driving vasodilation, vascular permeability, pain, and the molecular basis of hereditary angioedema and ACE-inhibitor cough.

StrongWell-Studied
Last updated 35 citations

What is Bradykinin?

Bradykinin is a 9-amino-acid endogenous peptide (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) and the prototypical member of the kinin family. It is not a wellness or research peptide that anyone 'takes' — it is a body-made signaling molecule that sits at the center of inflammation, vascular tone, pain, and several important pharmacology stories. Bradykinin is generated on demand by the proteolytic action of plasma kallikrein on high-molecular-weight kininogen, as part of the plasma contact system. A parallel tissue kinin system, involving tissue kallikrein acting on low-molecular-weight kininogen, generates lysyl-bradykinin (kallidin, the 10-residue sister peptide), which is then converted to bradykinin by plasma aminopeptidases. Both peptides act primarily at the constitutively expressed B2 bradykinin receptor (B2R), a Gq-coupled GPCR responsible for virtually all acute physiological bradykinin effects. A second receptor, B1R, is largely absent from healthy tissue but is strongly induced by inflammation, tissue injury, and cytokine exposure, and it preferentially binds the carboxypeptidase-generated metabolite des-Arg9-bradykinin rather than intact bradykinin. The system is tightly regulated by degradation: angiotensin-converting enzyme (ACE, kininase II), carboxypeptidase N (kininase I), and aminopeptidase P together clear more than 90% of circulating bradykinin, giving the peptide a plasma half-life of roughly 17-30 seconds. That short half-life and ACE's central role in clearance are what tie bradykinin to the side-effect profile of ACE inhibitors and, more consequentially, to hereditary angioedema.

What Bradykinin Is Investigated For

Bradykinin is a foundational physiology peptide rather than a therapeutic — it is not sold, dosed, or injected as a wellness agent, and any listing that frames it that way is wrong. Its importance is twofold. First, it is the body's main acute inflammatory vasoactive peptide: binding B2R on vascular endothelium, it triggers nitric-oxide-mediated vasodilation, opens endothelial junctions to let plasma leak into tissue (the classic edema response), sensitizes peripheral C-fiber nociceptors to produce inflammatory pain, and contracts bronchial smooth muscle. Second, it is the mechanistic hinge of three high-traffic clinical stories. Hereditary angioedema (HAE) is driven by uncontrolled bradykinin generation because patients with C1-inhibitor deficiency cannot restrain the contact-system activation that produces the peptide — which is why icatibant (a B2R antagonist) and the kallikrein inhibitors (lanadelumab, ecallantide, berotralstat) are the mechanism-specific HAE drugs. ACE-inhibitor cough (10-20% incidence with lisinopril, enalapril, and class-mates) is caused by bradykinin accumulating in the airways when ACE is blocked, sensitizing airway sensory nerves. Rare but dangerous ACE-inhibitor-induced angioedema involves the same mechanism, taken further. Around the edges, bradykinin has been implicated in sepsis-related capillary leak, acute pancreatitis, traumatic brain injury edema, and — in a widely discussed but never convincingly proven hypothesis — severe COVID-19 pulmonary edema. The honest framing is: bradykinin is one of the best-understood endogenous vasoactive peptides in medicine, and the interesting therapeutic story is not about giving bradykinin but about blocking it at the right level of the cascade.

Endogenous mediator of vasodilation and vascular permeability (not a therapeutic)
Strong90%
Principal driver of hereditary angioedema (HAE) attacks via uncontrolled B2R activation
Strong90%
Mechanism behind ACE-inhibitor cough (bradykinin accumulation in the airways)
Strong90%
Mechanism behind rare ACE-inhibitor-induced angioedema
Strong90%
Algesic and pro-nociceptive mediator (C-fiber sensitization in inflamed tissue)
Strong90%
Contributor to acute inflammation, edema, and bronchoconstriction
Strong90%
Proposed driver of COVID-19 pulmonary edema (bradykinin storm hypothesis)
Preliminary30%

History & Discovery

Bradykinin was discovered in 1949 by the Brazilian pharmacologist Mauricio Rocha e Silva, working with Wilson Teixeira Beraldo and Gastao Rosenfeld at the Biological Institute of Sao Paulo and the Butantan Institute (which is world-famous for its snake venom program). The three investigators were following up on the observation that snake venoms produced profound hypotension. Perfusing plasma globulins with venom from the Brazilian lanceheaded pit viper Bothrops jararaca, or with trypsin, they isolated a heat-stable factor that caused smooth muscle of the guinea-pig ileum to contract and lowered blood pressure in anesthetized animals. What set this factor apart from histamine and acetylcholine was the time course of its action — much slower in onset and longer in duration. They named it bradykinin from the Greek bradys ('slow') and kinein ('to move') — literally, 'the slow mover.' The primary report, 'Bradykinin, a hypotensive and smooth muscle stimulating factor released from plasma globulin by snake venoms and by trypsin,' appeared in the American Journal of Physiology in 1949. The 1950s and 1960s mapped the biochemistry. Elliott, Lewis, and Horton sequenced bradykinin as the nonapeptide Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg in 1960, making it one of the earlier peptides to be fully sequenced. Kallikreins — the proteases that cleave kininogen to release bradykinin — were characterized independently (the name comes from 'kallikreas,' Greek for pancreas, where the enzyme was first enriched). The related peptide kallidin (lysyl-bradykinin) was identified and shown to be generated by tissue kallikrein acting on low-molecular-weight kininogen, then converted to bradykinin by plasma aminopeptidases. By the late 1960s the system had a coherent outline: two kallikreins (plasma and tissue), two kininogens (high- and low-molecular-weight), two kinin products (bradykinin and kallidin), and a set of kininases that cleared them — ACE (kininase II) and carboxypeptidase N (kininase I) being the dominant ones in plasma. Receptor pharmacology matured in the 1970s and 1980s through the work of Domenico Regoli and colleagues in Sherbrooke, Quebec. Regoli's systematic structure-activity analyses of bradykinin analogs established that two distinct receptor subtypes existed — B1 and B2 — with different agonist preferences (B2 preferring intact bradykinin and kallidin, B1 preferring the carboxypeptidase-trimmed des-Arg metabolites) and different expression patterns (B2 constitutive, B1 inducible under inflammation). Both receptors were eventually cloned and classified as rhodopsin-family GPCRs, and the IUPHAR-NC formally codified the nomenclature in Leeb-Lundberg et al.'s 2005 Pharmacological Reviews paper. The drug-development arc has produced one approved receptor-directed therapy — icatibant (HOE 140), the peptidase-resistant B2R antagonist developed at Hoechst in the early 1990s and approved for hereditary angioedema in the EU (2008) and US (2011). The larger HAE armamentarium — ecallantide (plasma kallikrein inhibitor), lanadelumab (monoclonal kallikrein inhibitor), berotralstat (oral kallikrein inhibitor), and C1-inhibitor concentrate replacement — all derive from the bradykinin mechanistic story. Attempts to develop bradykinin-related therapies for other indications (sepsis, traumatic brain injury, cancer pain, COVID-19) have not yet produced a successful drug. Bradykinin itself remains what it has always been: an endogenous signaling peptide of extraordinary pharmacological reach, characterized with unusual thoroughness and exploited therapeutically almost entirely by blocking it rather than by administering it.

How It Works

Bradykinin is a tiny peptide the body makes on the fly when tissue is injured or inflamed. It tells blood vessels to dilate and leak fluid (producing swelling), excites pain nerves (making inflammation hurt), and contracts airway smooth muscle. The body normally keeps bradykinin in check by chewing it up quickly with enzymes — most importantly ACE, the same enzyme that blood-pressure drugs like lisinopril target. When ACE is blocked, bradykinin lingers longer, which is why some people on ACE inhibitors get a dry cough or, rarely, facial swelling. A related genetic condition called hereditary angioedema produces runaway bradykinin; the drugs that treat it either stop bradykinin from being made or block it at its receptor.

Bradykinin is produced by the kinin-kallikrein system, which has two parallel arms. In the plasma arm, activation of Factor XII on negatively charged surfaces (traditionally glass, but in vivo endothelial surfaces, collagen, misfolded proteins, and certain pathogen components) converts prekallikrein to plasma kallikrein; plasma kallikrein then cleaves high-molecular-weight kininogen to release bradykinin. In the tissue arm, tissue kallikrein cleaves low-molecular-weight kininogen to release kallidin (lysyl-bradykinin), which plasma aminopeptidases rapidly trim to bradykinin. The system is restrained by C1 inhibitor (C1-INH), the principal plasma inhibitor of both activated Factor XII and plasma kallikrein — which is why C1-INH deficiency produces the uncontrolled bradykinin generation of hereditary angioedema. Once generated, bradykinin binds two G-protein-coupled receptors of the rhodopsin family. The B2 receptor (B2R, BDKRB2) is constitutively expressed on vascular endothelium, smooth muscle, sensory neurons, epithelial cells, and many other tissues, and it mediates essentially all acute physiological bradykinin effects. B2R is predominantly Gq-coupled: activation stimulates phospholipase C-beta, generates IP3 and diacylglycerol, releases intracellular Ca2+ from IP3-sensitive stores, and activates protein kinase C. In endothelium, the Ca2+/calmodulin signal combined with direct phosphorylation events activates endothelial nitric oxide synthase (eNOS, at Ser1177) and also triggers release of prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) — producing the characteristic vasodilation. The same cascade phosphorylates endothelial junction proteins, opening intercellular gaps and increasing vascular permeability, the direct cause of bradykinin-driven edema. On C-fiber nociceptors, B2R signaling closes M-type K+ channels, opens Ca2+-activated Cl- channels, and sensitizes TRPV1, producing acute excitation and heightened responsiveness to thermal and mechanical stimuli — the molecular basis of inflammatory pain. The B1 receptor (B1R, BDKRB1) is expressed at very low levels in healthy tissue but is strongly induced by pro-inflammatory cytokines (IL-1beta, TNF-alpha), tissue injury, and endotoxin. B1R binds intact bradykinin poorly but is strongly activated by the carboxypeptidase-N- and carboxypeptidase-M-generated metabolite des-Arg9-bradykinin (and by des-Arg10-kallidin from the tissue arm). B1R is also Gq-coupled, and its inducible expression makes it particularly relevant to chronic inflammation, neuropathic pain, and some features of diabetes complications. Degradation is fast and enzymatically redundant. ACE (kininase II) removes a C-terminal dipeptide to inactivate bradykinin and accounts for the majority of plasma clearance — quantitative studies attribute roughly 52% of kininase activity to ACE, 25% to aminopeptidase P, and 16% to carboxypeptidase N. The plasma half-life is on the order of 17-34 seconds. This rapid clearance is why ACE inhibition produces meaningful elevations in tissue bradykinin (enough to sensitize airway cough receptors), why HAE attacks can be self-limited once kallikrein activation subsides, and why any exogenous peptidic therapy directed at the bradykinin system has to be engineered for peptidase resistance — icatibant's five non-proteinogenic amino acid substitutions exist for exactly this reason.

Evidence Snapshot

Overall Confidence90%

Human Clinical Evidence

Extensive and mature. Bradykinin's human physiology, its role in ACE-inhibitor cough and angioedema, and its central role in hereditary angioedema are well established. HAE management guidelines, the FAST trial program for icatibant, and the broader kallikrein-inhibitor class (lanadelumab, berotralstat, ecallantide) all rest on the bradykinin-B2R mechanism. Human pain and inflammation studies have directly demonstrated bradykinin's algesic and pro-edematous effects. The one clinical story that did not pan out was the 'bradykinin storm' hypothesis of severe COVID-19.

Animal / Preclinical

Extensive. Nearly eight decades of preclinical research — from Rocha e Silva's 1949 identification to modern B1R- and B2R-knockout models — have characterized the kinin-kallikrein system more thoroughly than almost any endogenous peptide pathway. Pain, inflammation, vascular permeability, airway reactivity, and cardioprotection models are all well-developed.

Mechanistic Rationale

Very strong. The kinin-kallikrein cascade, the distinct B1 and B2 receptor pharmacology, the enzymatic degradation pathway, and the downstream Gq-PLC-Ca2+-NO signaling are among the best-mapped endogenous-peptide pathways in physiology.

Research Gaps & Open Questions

What the current literature has not yet settled about Bradykinin:

  • 01Whether B1 receptor antagonists can deliver safe and effective analgesia for chronic inflammatory or neuropathic pain — preclinical rationale is strong, multiple B1R antagonists have entered early clinical trials, but none has yet reached approval.
  • 02The role of kinins in sepsis, capillary-leak syndrome, acute pancreatitis, and traumatic brain injury — mechanistically plausible involvement that has not produced a confirmed therapeutic target despite multiple investigational programs.
  • 03The fate of the 'bradykinin storm' hypothesis of severe COVID-19 — mechanistically interesting but clinically unconfirmed by randomized trials of bradykinin-targeted agents.
  • 04Tissue-kallikrein-kinin pathway contributions to cardiovascular, renal, and diabetic complications — long hypothesized to be cardioprotective and nephroprotective, but the clinical relevance of modulating this arm (as opposed to the plasma contact system) is not fully resolved.
  • 05Whether cancer biology co-opts the kinin system — B1R and B2R are expressed in some tumors, bradykinin can drive tumor-associated vascular permeability and possibly proliferation, but the therapeutic implications are early.
  • 06How interindividual variation in kininase activity (ACE, aminopeptidase P, carboxypeptidase N polymorphisms) accounts for differential susceptibility to ACE-inhibitor cough and angioedema — genetic and enzymatic studies exist but risk prediction is not clinically actionable.
  • 07Long-term consequences of chronic low-grade bradykinin signaling elevation in patients on long-term ACE inhibitor therapy — tempered by the robust cardiovascular mortality benefit of these drugs, but the fine-grained tradeoffs are incompletely characterized.

Forms & Administration

Bradykinin is not a therapeutic peptide and has no approved route of administration for humans. In research settings, synthetic bradykinin and its analogs (des-Arg9-bradykinin for B1R studies, selective B2R agonists and antagonists for pharmacology) are used as laboratory reagents — typically in isolated tissue preparations, in vitro receptor studies, or under carefully controlled IV infusion in human physiology protocols where the goal is to characterize the vasoactive or sensory response. There is no wellness-peptide, injectable, oral, intranasal, or topical bradykinin product in any regulated market. What does exist in clinical use are drugs that modulate the bradykinin system: icatibant (subcutaneous B2R antagonist, approved for HAE attacks), ecallantide (subcutaneous plasma kallikrein inhibitor, approved for HAE attacks), lanadelumab (subcutaneous monoclonal plasma kallikrein inhibitor, approved for long-term HAE prophylaxis), berotralstat (oral plasma kallikrein inhibitor, approved for long-term HAE prophylaxis), and C1-inhibitor concentrates (Cinryze, Berinert, Haegarda, Ruconest) for replacement therapy. If you are looking at a product marketed as 'bradykinin peptide' for wellness or anti-aging use, it does not correspond to a legitimate therapeutic category.

Common Questions

Safety Profile

Safety Information

Common Side Effects

Not applicable in the wellness-peptide sense — bradykinin is endogenous and not self-administeredDirect IV bradykinin infusion in research settings produces pronounced flushing, headache, transient hypotension, reflex tachycardia, and burning pain at the infusion siteElevated endogenous bradykinin (e.g., from ACE inhibitor use) can produce persistent dry cough in 10-20% of patientsRare ACE-inhibitor-induced angioedema (approximately 0.1-0.7% incidence, higher in Black patients) is a bradykinin-driven adverse effectInflammatory pain, edema, and bronchoconstriction are physiologically 'expected' effects of locally elevated bradykinin at sites of tissue injury

Cautions

  • Bradykinin is a research reagent and endogenous mediator, not a therapy — there is no legitimate wellness-peptide context for administering it
  • Claims that exogenous bradykinin is useful for vasodilation, circulation, or similar should be treated with strong skepticism given its minutes-scale degradation and potent adverse-effect profile
  • Conditions where bradykinin signaling is already elevated or pathological — hereditary angioedema, active ACE-inhibitor angioedema, uncontrolled anaphylaxis, severe sepsis — are the wrong settings to add any bradykinin substrate or mimetic
  • The clinically useful pharmacology in this space is directed at reducing or blocking bradykinin signaling (icatibant, lanadelumab, berotralstat, ecallantide, C1-INH replacement), not supplementing it

What We Don't Know

The B1 receptor arm of kinin signaling — induced under inflammation and chronic tissue injury, and preferentially activated by the des-Arg9-bradykinin metabolite — remains incompletely mapped clinically. B1 antagonists have shown preclinical activity in pain, diabetes complications, and inflammation but have not yet produced an approved drug. The role of bradykinin in sepsis, capillary-leak syndromes, acute pancreatitis, traumatic brain injury, and severe COVID-19 is mechanistically plausible but clinically unresolved, and the bradykinin-storm framing of severe COVID-19 in particular did not translate into a confirmed therapeutic target.

Myths & Misconceptions

Myth

Bradykinin is a peptide you can buy and inject for vasodilation or circulation benefits.

Reality

It is not. Bradykinin is an endogenous signaling peptide with a plasma half-life of seconds, produced on demand by kallikrein cleavage of kininogen at sites of tissue injury or contact-system activation. There is no FDA-approved or equivalently-regulated exogenous bradykinin product in any regulated market. Any product marketed as 'bradykinin peptide' for wellness, anti-aging, or circulation does not correspond to a legitimate therapeutic category, and injecting or infusing exogenous bradykinin would produce pronounced flushing, hypotension, edema, and inflammatory pain rather than any useful 'vascular benefit.' The clinically useful pharmacology in this space blocks bradykinin, not supplements it.

Myth

Hereditary angioedema is an allergic reaction, and bradykinin is just one of many mediators involved.

Reality

HAE is specifically and predominantly a bradykinin-driven disease, not an allergic reaction. Attacks happen because C1-inhibitor deficiency allows unchecked plasma kallikrein activation, producing excess bradykinin that engages the B2 receptor on vascular endothelium. Histamine, leukotrienes, and mast-cell mediators are not meaningfully involved. That is why the allergic-angioedema toolkit — antihistamines, corticosteroids, and epinephrine — is ineffective for HAE, and why bradykinin-targeted drugs (icatibant, ecallantide, lanadelumab, berotralstat, C1-INH replacement) are the only mechanistically appropriate therapies.

Myth

ACE inhibitor cough is a minor, unrelated side effect unrelated to bradykinin.

Reality

ACE-inhibitor cough is mechanistically a bradykinin phenomenon. ACE is the single largest bradykinin-degrading enzyme in plasma and airway tissue; when ACE is blocked, bradykinin (and substance P) accumulate in the upper airway and sensitize cough receptors and C-fibers, producing the characteristic dry cough that affects roughly 10-20% of patients on the drug class. This is why the cough does not respond to cough suppressants but resolves reliably within weeks of discontinuing the ACE inhibitor — and why switching to an angiotensin-receptor blocker (which does not affect bradykinin metabolism) almost always eliminates the cough.

Myth

Bradykinin and bradykinin antagonists are interchangeable concepts — if bradykinin is 'bad,' then blocking it is always good.

Reality

Bradykinin is not simply 'bad.' At physiological levels, B2 receptor signaling contributes to normal vascular tone, endothelial nitric oxide production, natriuresis, and cardioprotection during ischemia — part of the reason ACE inhibition is cardioprotective is believed to be its preservation of bradykinin-mediated beneficial effects alongside the reduction in angiotensin II. Wholesale, chronic B2R blockade in otherwise healthy people would not be without cost. The clinical logic for bradykinin antagonism (icatibant) applies to states of pathological bradykinin excess — specifically HAE attacks — not to routine modulation of normal physiology.

Myth

The 'bradykinin storm' hypothesis proved that bradykinin drives severe COVID-19.

Reality

It did not. The 2020 eLife paper by Garvin and colleagues proposed, on the basis of computational modeling, that SARS-CoV-2-driven ACE2 dysregulation could produce a bradykinin storm responsible for COVID-19 pulmonary edema. It was a mechanistically interesting hypothesis that generated substantial follow-up work, including small trials of icatibant and kallikrein inhibitors in COVID-19. The clinical signal has been underwhelming — no large randomized trial has demonstrated a convincing efficacy of bradykinin-targeted therapy in severe COVID-19, and subsequent reviews have been skeptical that bradykinin is a major driver of severe disease relative to the dominant cytokine and complement mechanisms. The hypothesis was a provocation, not a proof.

Published Research

35 studies

Bradykinin receptor expression and bradykinin-mediated sensitization of human sensory neurons

Original ResearchPMID: 37703419

A Comprehensive Review of Bradykinin-Induced Angioedema Versus Histamine-Induced Angioedema in the Emergency Department

ReviewPMID: 36579009

Function and structure of bradykinin receptor 2 for drug discovery

ReviewPMID: 36109717

A new storm on the horizon in COVID-19: Bradykinin-induced vascular complications

ReviewPMID: 33358968

Pulmonary edema in COVID-19: Explained by bradykinin?

ReviewPMID: 33077247

A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm

Garvin et al. 2020 (eLife) — the influential computational-modeling paper that proposed a 'bradykinin storm' downstream of SARS-CoV-2-driven dysregulation of the renin-angiotensin system as a mechanism for severe COVID-19 pulmonary edema. Generated substantial follow-up work but did not translate into a convincing therapeutic signal from bradykinin-targeted interventions.

Hypothesis / Computational ModelingPMID: 32633718

A Review of the Role of Bradykinin and Nitric Oxide in the Cardioprotective Action of Angiotensin-Converting Enzyme Inhibitors: Focus on Perindopril

ReviewPMID: 31646466

The bradykinin-forming cascade and its role in hereditary angioedema

Kaplan and Joseph's comprehensive account of the plasma contact-system pathway by which C1-inhibitor deficiency permits uncontrolled kallikrein activation and excess bradykinin generation in HAE. The mechanistic foundation for bradykinin-targeted HAE therapy.

ReviewPMID: 20377108

The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+-activated Cl- channels

Original ResearchPMID: 20335661

Excitation and sensitization of nociceptors by bradykinin: what do we know?

ReviewPMID: 19396590

Bradykinin, a hypotensive and smooth muscle stimulating factor released from plasma globulin by snake venoms and by trypsin

Rocha e Silva, Beraldo, and Rosenfeld 1949 (American Journal of Physiology) — the foundational paper in which the Brazilian group working with snake venom from Bothrops jararaca at the Butantan Institute identified the 'slow-acting' hypotensive and smooth-muscle-stimulating factor released from plasma globulin by trypsin and snake venom, and named it bradykinin from the Greek bradys ('slow') and kinein ('to move'). Every downstream kinin-system result traces back to this discovery.

Original ResearchPMID: 18127230

Bradykinin and peripheral sensitization

ReviewPMID: 16497159

Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based clinical practice guidelines

ACCP evidence-based guideline synthesizing the bradykinin-and-substance-P-mediated mechanism of ACE-inhibitor cough (10-20% incidence across the class), clinical characteristics (dry, non-productive, resolves within 1-4 weeks of discontinuation), and management (switch to an angiotensin receptor blocker, which does not affect bradykinin metabolism). The standard clinical reference.

Clinical GuidelinePMID: 16428706

Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission

Original ResearchPMID: 16135755

International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences

Leeb-Lundberg et al. 2005 (Pharmacological Reviews) — the authoritative IUPHAR nomenclature review establishing the B1 and B2 kinin receptor subtypes, their distinct pharmacology (B2R constitutive and preferring bradykinin/kallidin; B1R inducible and preferring the des-Arg metabolites), and their roles across cardiovascular, inflammatory, and nociceptive physiology. The standard reference for kinin receptor classification.

ReviewPMID: 15734727

Bradykinin receptor ligands: therapeutic perspectives

ReviewPMID: 15459675

Rapid increase in endothelial nitric oxide production by bradykinin is mediated by protein kinase A signaling pathway

Original ResearchPMID: 12821139

Post-translational mechanisms of endothelial nitric oxide synthase regulation by bradykinin

ReviewPMID: 12489789

B2 receptor-mediated enhanced bradykinin sensitivity of rat cutaneous C-fiber nociceptors during persistent inflammation

Original ResearchPMID: 11731532

Pathways of bradykinin degradation in blood and plasma of normotensive and hypertensive rats

Quantitative enzymology showing that ACE accounts for roughly 52% of plasma kininase activity, aminopeptidase P 25%, and carboxypeptidase N 16% — together clearing more than 90% of bradykinin and giving the peptide its ~17-30 second plasma half-life. The empirical basis for why ACE inhibition raises bradykinin tone.

Original ResearchPMID: 11299220

Kinin B(1) receptors and the cardiovascular system: regulation of expression and function

ReviewPMID: 11054467

Kallidin- and bradykinin-degrading pathways in human heart: degradation of kallidin by aminopeptidase M-like activity and bradykinin by neutral endopeptidase

Original ResearchPMID: 10209002

Bradykinin receptors and their antagonists

ReviewPMID: 9650825

Bradykinin inhibits M current via phospholipase C and Ca2+ release from IP3-sensitive Ca2+ stores in rat sympathetic neurons

Original ResearchPMID: 9618544

Endothelial function and bradykinin in humans

ReviewPMID: 9429844

Bradykinin receptors

ReviewPMID: 9112069

Bradykinin-evoked sensitization of airway sensory nerves: a mechanism for ACE-inhibitor cough

Original ResearchPMID: 8673930

Bradykinin and inflammatory pain

ReviewPMID: 7681240

Pharmacology of bradykinin and related kinins

ReviewPMID: 6134437

The effect of kinin agonists and antagonists on the pain response of the human blister base

Original ResearchPMID: 3444481

Mechanism of digestion of bradykinin and lysylbradykinin (kallidin) in human serum. Role of carboxypeptidase, angiotensin-converting enzyme and determination of final degradation products

Original ResearchPMID: 2539165

Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology

ReviewPMID: 1616218

Mauricio Rocha e Silva and the discovery of bradykinin

Historical ReviewPMID: 1609634

Bioregulation of kinins: kallikreins, kininogens, and kininases

Bhoola, Figueroa, and Worthy 1992 (Pharmacological Reviews) — the comprehensive and widely cited review that laid out the kinin-kallikrein system in integrated form: the two kallikrein arms, kininogen substrates, and the kininase degradation pathway. Still a foundational reference for the molecular organization of the system.

ReviewPMID: 1313585

Bradykinin-degrading enzymes: structure, function, distribution, and potential roles in cardiovascular pharmacology

ReviewPMID: 1282629

Quick Facts

Class
Kinin / Vasoactive Peptide
Evidence
Strong
Safety
Well-Studied
Updated
Apr 2026
Citations
35PubMed

Also known as

BKKallidin-9Des-Arg10-bradykinin (metabolite)Bradykinin 1-9

Tags

Endogenous PeptideVasodilatorInflammatory MediatorKinin SystemPain SignalingHereditary Angioedema

Related Goals

Evidence Score

Overall Confidence90%

Clinical Trials

View Clinical Trials

Links to ClinicalTrials.gov for reference. Listing does not imply endorsement.