Morphological and physiological correlation of bradykinin-induced macromolecular efflux

Bradykinin applied topically for 4 min produced marked dose-related increases in the number of fluorescent dextran (mol wt 145,000) vascular leakage sites exclusively from small postcapillary venules--evidence for an increase in macromolecular permeability. The increase in macromolecular permeability was short-lived, making repeated applications possible. The number of bradykinin-induced venular fluorescent dextran leakage sites could be greatly reduced by the simultaneous topical application of isoproterenol, and this antagonism of the increase in macromolecular permeability could be prevented by pretreatment with propranolol. The topical application of papaverine failed to antagonize the increase in the number of venular leakage sites of fluorescent dextran by bradykinin. A continuous 90-min superfusion of bradykinin elicited an initial marked increase in the number of fluorescent dextran venular leakage sites, which then waned after 20-30 min, returning to near control despite the continued superfusion with bradykinin. In canine forelimbs the bradykinin-induced increase in protein efflux, total protein transport, and lymph flow also peaked in approximately 30 min and then waned markedly despite continued local intra-arterial infusions of this agent for prolonged periods. The morphological data from the cheek pouch agrees well with the physiological data from the forelimb, suggesting that an increase in protein efflux in the canine forelimb could be readily explained by an increase in the number of large pores.