Bradykinin

Summary

Bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) is an endogenous nonapeptide kinin generated from kininogen by kallikrein cleavage. It plays key roles in inflammation, pain, vasodilation, and blood pressure regulation. It is used primarily as a pharmacological tool and research agent rather than a therapeutic drug; however, it is clinically relevant as the mediator of ACE inhibitor-induced angioedema and cough.

Mechanism of Action

Bradykinin is an endogenous nonapeptide that binds to B1 and B2 bradykinin receptors (GPCRs), activating phospholipase C, increasing intracellular calcium, and stimulating nitric oxide synthase and prostaglandin synthesis, leading to vasodilation, increased vascular permeability, smooth muscle contraction, and pain sensitization.

Routes of Administration

Goals & Uses

• Wound healing / tissue repairRegenerativeLow
• Vasodilation / blood pressure reductionCardiovascularHigh
• Research tool for pain sensitizationNeuroscience / ResearchHigh
• Cardioprotection (ischemic preconditioning)CardiovascularModerate
• Provocative testing (bronchial / vascular)DiagnosticModerate

Contraindications

• Severe asthma / BronchospasmRespiratoryHigh
• History of bradykinin-mediated angioedemaAllergic / ImmunologicHigh
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Hypotension / Hemodynamic instabilityCardiovascularHigh

Adverse Effects

• Tachycardia (reflex)CardiovascularUncommon
• HypotensionCardiovascularCommonLow blood pressure
• FlushingVascularCommonWarmth and redness of the skin
• BronchoconstrictionRespiratoryUncommon
• Pain / Burning sensationNeurologicalCommon
• AngioedemaImmunologicRare

Drug Interactions

• NSAIDs (e.g., indomethacin, ibuprofen)Moderate
• Angiotensin Receptor Blockers (ARBs)Low
• Nitrates / Nitric oxide donorsModerate
• ACE Inhibitors (e.g., enalapril, lisinopril)High

Population Constraints

• Elderly patientsAgeRelative
• Patients on ACE inhibitor therapyPharmacologicalAbsolute
• Pregnant womenReproductiveRelative
• Patients with hereditary angioedema (HAE)Genetic / ImmunologicAbsolute
• Asthmatic patientsRespiratoryRelative

Regulatory Status

• European UnionUnapprovedNot approved as a therapeutic by EMA. Used in research contexts. Icatibant (B2 antagonist) is EMA-approved for HAE.
• United StatesUnapprovedNot an FDA-approved therapeutic agent. Used as research compound and pharmacological tool. Bradykinin receptor antagonists (icatibant) are FDA-approved for HAE.
• United KingdomUnapprovedNot approved by MHRA as a therapeutic. Research use only.

Bradykinin itself is not an approved therapeutic agent in any major jurisdiction. It is used as a research tool and in diagnostic/provocative testing contexts. Its antagonists (e.g., icatibant) and the bradykinin pathway are major therapeutic targets for hereditary angioedema.

Evidence & Sources

No sources recorded yet.