COAGULATION IN-VIVO MICROCIRCULATION AND IN-VITRO CAUSED BY ENDOTHELIN-1

This study was designed to elucidate the participation of endothelin-1(ET-1) in vivo and in vitro coagulation. The microvascular hemodynamic changes in terms of intravascular thrombus formation in rat mesentery induced by the superfusion of ET-1 (0.5, 1 and 2 pmol) were visualized by an intravital microscope system assisted by television-video tape recorder system. In addition to vasoconstriction we observed the blockade of circulation by clumps resembling thrombus in a dose dependent fashion by ET-1. Thrombus formation could be attenuated by pretreatment with superfusion of 3.8% Na citrate solution but not by the prior superfusion of 1 to 3 ng of nitroglycerine. Thrombus formation was found after the administration of 10 mul of CaCl2 (100nM) solution in Na citrate (3.8%, 20 mul) and ET-1 treated field. In vitro study, a dose dependent increase in TAT (thrombin-antithrombin complexes) and decrease in AT III (antithrombin III) (%) activity, the prolongation of PT (prothrombin time) and APTT (activated partial thromboplastin time) was found by administering ET-1 immediately in native (unanticoagulated) blood in silicon coated test tubes (p<0.05; n=6). However in citrated blood, TAT complexes, AT III (%) activity, PT and APTT were not significantly changed after administration of the same doses of ET-1 (p>0.05; n=6). Therefore, this study suggested that endothelin-1 caused intravascular thrombosis and enhanced intra test tube coagulation which could be attenuated by blocking ionic calcium.