Thrombin increases fluid flux in isolated rat lungs by a hemodynamic and not a permeability mechanism. Waypa, Gregory B., Peter A. Vincent, Christine A. Morton, and Fred L. Minnear. Department of Physiology and Cell Biology, Albany Medical College, Albany, NY
APStracts 2:0508A, 1995.
[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 if thrombin increases endothelial permeability of the isolated, perfused rat lung and if a change in permeability or hemodynamics mediates the gain in lung weight. Endothelial protein permeability was assessed by regression analysis of 125I-albumin clearance vs fluid flux to determine the permeability-surface area product (PS) and the reflection coefficient ([sigma]). Thrombin (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 increase in transvascular fluid flux as depicted by a gain in lung weight. Pulmonary arterial and capillary pressures and arterial and venous resistances increased by 10 min after thrombin injection, and lung weight decreased due to arterial constriction. From 10 to 50 min, pressures and resistances decreased, but capillary pressure and venous resistance decreased to a lesser extent and as a result lung weight increased. Pretreatment with BQ-123, an endothelin receptor (ETA) antagonist, attenuated the sustained increases in pressures and resistances and the rate of lung weight gain. Indomethacin, a cyclooxygenase inhibitor, had no effect. These findings indicate that the increase in lung weight induced by thrombin results from an elevation of capillary pressure mediated, in part, by endothelin and is not due to an increase in endothelial protein permeability of the isolated, perfused rat lung. 

Received 17 July 1995; accepted in final form 9 November 1995.
APS Manuscript Number A768-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95