Bradykinin

Bradykinin is an endogenous nonapeptide generated from kininogens by the enzyme kallikrein. It is a potent vasodilator and pain-sensitizing mediator involved in inflammation, blood pressure regulation, and the pain cascade. Its receptor antagonist Icatibant is FDA-approved for treatment of hereditary angioedema (HAE), validating the clinical significance of this kinin pathway.

Bradykinin acts on two G-protein-coupled receptors: B1 (inducible, involved in chronic inflammation) and B2 (constitutively expressed, mediates acute effects). B2 receptor activation stimulates phospholipase C, increases intracellular calcium, triggers nitric oxide synthase, and releases prostaglandins. These combined effects produce vasodilation, increased vascular permeability, smooth muscle contraction, and sensitization of nociceptors underlying pain and inflammation.

Bradykinin is extensively studied in cardiovascular physiology, pain research, and inflammatory disease. Its role in ACE inhibitor-induced cough (potentiation of bradykinin via reduced degradation) is well established. Icatibant, a B2 receptor antagonist, received FDA approval in 2011 for HAE. Ongoing research examines bradykinin's role in COVID-19 pathophysiology and potential therapeutic targets in the kinin-kallikrein system.