THROMBIN INCREASES FLUID FLUX IN ISOLATED RAT LUNGS BY A HEMODYNAMIC AND NOT A PERMEABILITY MECHANISM

alpha-Thrombin increases endothelial protein permeability in vitro and induces weight gain in the isolated perfused lung. The objectives of this study were to determine whether thrombin increases endothelial pe rmeability of the isolated perfused rat lung and whether a change in p ermeability or hemodynamics mediates the gain in lung weight. Endothel ial protein permeability was assessed by regression analysis of I-125- labeled albumin clearance vs. fluid flux to determine the permeability surface area product (PS) and the reflection coefficient (sigma). Thr ombin (5 x 10(-8) or 5 x 10(-7) M) did not alter protein permeability from the control values of PS and sigma. Thrombin caused an overall in crease in transvascular fluid flux, as depicted by a gain in lung weig ht. Pulmonary arterial and capillary pressures and arterial and venous resistances increased by 10 min after thrombin injection, and lung we ight decreased due to arterial constriction. From 10 to 50 min, pressu res and resistances decreased, but capillary pressure and venous resis tance decreased to a lesser extent and, as a result, lung weight incre ased. Pretreatment with BQ-123, an endothelin-receptor antagonist, att enuated the sustained increases in pressures and resistances and the r ate of lung weight gain. Indomethacin, a cyclooxygenase inhibitor, had no effect. These findings indicate that the increase in lung weight i nduced by thrombin results from an elevation of capillary pressure med iated, in part, by endothelin and is not due to an increase in endothe lial protein permeability of the isolated perfused rat lung.