Experimental hypothyroidism increases plasminogen activator inhibitor activity in rat plasma

The aim of the present study was to investigate whether hypothyroidism would affect the components of the rat plasma fibrinolytic system. Hypothyroidism was induced by feeding rats a thiouracil-containing diet for 2 weeks. During this period, half of the animals received subcutaneous injections of L-thyroxine (20 micrograms/kg daily) to restore thyroid hormone levels. Groups of euthyroid rats were similarly treated with L-thyroxine. Plasma tissue-type PA (t-PA) activity was not affected by thyroid status. Plasma urokinase-type PA (u-PA) activity was significantly decreased by the thiouracil-containing diet; however, this effect was not abolished by L-thyroxine. Plasminogen, alpha 2-antiplasmin and fibrinogen were not affected by hypothyroidism. In the hypothyroid group, plasma PAI activity was significantly increased; no such increase was found in animals simultaneously receiving L-thyroxine. Plasma PAI activity correlated with T3 (r = -0.586; P < 0.005) and cholesterol (r = +0.737; P < 0.001); in multiple regression analysis, however, the correlation between PAI activity and T3 was not significant. The increase in plasma PAI activity during hypothyroidism may thus not be a direct effect of the thyroid hormone, but an indirect one through some other, possibly cholesterol related, component.