FUROSEMIDE ENHANCES BLOOD FIBRINOLYTIC-ACTIVITY IN RATS WITH NO CORRELATION TO ITS DIURETIC ACTIVITY

Furosemide is a diuretic compound with in vivo profibrinolytic propert ies. This study was designed to elucidate the mechanism of the enhance d blood fibrinolytic activity and its in vivo relevance after oral adm inistration of furosemide to rats. The diuretic activity was not affec ted at a dose of 10 mg/kg but was increased about 4-fold at a dose of 25 mg/kg with a maximal effect 2 h after administration. Owing to the diuretic properties of furosemide a 5% increased packed cell volume as well as in the numbers of erythrocytes and platelets were measured at a dose of 30 mg/kg. These effects were not observed up to doses of 10 mg/kg, Furosemide administration to rats (2 h before brood sampling) resulted in a dose-dependent increase in ex vivo measured blood clot l ysis from 141 +/- 13% up to 229 +/- 27% (mean +/- SEM; n = 6) of contr ol lysis rates at doses of 3 and 30 mg/kg, respectively. These doses w ere also studied in a venous thrombosis model. Experimentally induced venous thrombosis as measured by their thrombus size was reduced to 72 +/- 7% and 49 +/- 6% (mean +/- SEM; n = 6) of control values at 3 and 30 mg/kg, respectively, Up to 10 mg/kg no significant effects on plas ma tissue type plasminogen activator (t-PA) and urokinase-type plasmin ogen activator (u-PA) activity levels could be detected as well as on plasma t-PA antigen levels. The 30 mg/kg significantly affected PAI-1 levels (reduction to 94%) as well as t-PA activity and antigen levels (increased by 24 +/- 6% (n = 6; mean +/- SEM) and 44 +/- 15% (n = 5; m ean +/- SEM)), With the solid-phase fibrinolytic assay we showed that, upon furosemide treatment, an increased fibrinolytic activity could b e measured of 155 and 198% at doses of 10 and 30 mg/kg respectively re lative to blood of control treated rats which could be neutralized wit h antibodies against t-PA. it is concluded that furosemide dose depend ently increases blood fibrinolytic activity which is correlated to blo od t-PA activity but not to its diuretic activity.