Bradykinin causes a prolonged increase in skin microvascular permeability

Bradykinin is an endogenous inflammatory mediator, and its mechanism of action is incompletely understood. It is controversial whether bradykinin causes a sustained increase in microvascular permeability, or has only a transient effect. In anesthetized dogs intraarterial infusion of bradykinin (0.14 to 0.54 μg/kg/min) produced an immediate increase in flow of protein-rich, hindpaw lymph. After 210 min of bradykinin infusion lymph flow was threefold greater than baseline, lymph protein concentration remained doubled, and in a dose-related fashion bradykinin produced a sustained increase in lymph protein flux. Lymph flow was then further increased with venous hypertension, and after 4 hr lymph protein flux remained greater from the bradykinin paws than from the control paws. This sustained increase in protein flux indicates that bradykinin produces an increase in permeability at the microvascular membrane by a mechanism that is different from how the initial increase in permeability was produced.