bradykininmediated

Bradykinin-mediated describes biological effects driven by bradykinin, a nonapeptide produced in the kallikrein-kinin system. Bradykinin is generated from high-molecular-weight kininogen by tissue kallikrein and plasma kallikrein. It signals mainly through the bradykinin B2 receptor, which is constitutively expressed, while the B1 receptor is induced during inflammation.

Activation of B2 receptors on vascular endothelium causes rapid vasodilation and increased vascular permeability, leading to redness, warmth, and edema. Permeability changes involve endothelial contraction and disruption of adherens junctions, and exposure of subendothelial tissues contributes to edema formation. Bradykinin also sensitizes nociceptors, contributing to pain. Its effects are rapidly terminated by peptidases, including angiotensin-converting enzyme (ACE), neutral endopeptidases, and aminopeptidases.

Clinical significance: Bradykinin-mediated edema is a hallmark of hereditary angioedema due to C1 esterase inhibitor deficiency or dysfunction, and less often of ACE-inhibitor–associated angioedema. Unlike histamine-mediated angioedema, bradykinin-driven swelling often lacks itching and responds poorly to standard antihistamines. Airway involvement requires urgent management.

Management and therapy: Specific therapies target the bradykinin pathway, including icatibant, a selective B2 receptor antagonist, and kallikrein inhibitors such as ecallantide. Treatment of ACE-inhibitor–related angioedema may involve stopping the ACE inhibitor and providing supportive care; plasma-derived C1-INH concentrates can be used in some cases. Diagnostic workup may assess C1-INH function and complement components; measuring bradykinin levels is not routine.

Research directions: Ongoing work includes broader understanding of bradykinin signaling in inflammation and development of new receptor antagonists, with emphasis on safer management of bradykinin-mediated edema in diverse conditions.