BRADYKININ AND TUMOR-NECROSIS-FACTOR-ALPHA ALTER ALBUMIN TRANSPORT IN-VIVO - A COMPARATIVE-STUDY

These studies indicate that tumor necrosis factor-alpha (TNF alpha) al ters albumin permeability and unlike bradykinin (BK) the increased alb umin permeability lasts for the duration of the application. Neither a gonist requires the presence of white blood cells or other blood-borne substances to produce this inflammatory response. These experiments w ere completed in the in situ, microcannulated, perfused venules of the mesentery in the anesthetized hamster. Albumin transport was measured using intravital fluorescence microscopy, TRITC-labeled albumin, and densitometric tracking. Further, by varying the intravascular pressure , the hydraulic (L-p(1 - sigma)) and diffusive permeability (P-0) coef ficients of these microvessels were determined. Both BK and TNF alpha produced an increase in albumin flux, which was dependent upon the dos e and time domains. This response was present when the agonists were g iven by either intra-or extravascular presentation. Both hydraulic cou pling and microvascular permeability were increased by BK and TNF alph a. TNF alpha increased albumin permeability rapidly and its effect las ted as long as TNF alpha was present, whereas the increased albumin tr ansport by BK was biphasic. The results implicate a dynamic modificati on in the microvascular wall to these inflammatory agonists and the me chanism(s) for transduction in the endothelium are quite different. (C ) 1997 Academic Press.