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Thromb Haemost 1992; 67(06): 697-701
DOI: 10.1055/s-0038-1648525
Original Articles
Schattauer GmbH Stuttgart

On the Fibrinolytic System in Aged Rats, and Its Reactivity to Endotoxin and Cytokines

J J Emeis
The Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands
,
A Brouwer
The Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands
,
R J Barelds
The Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands
,
M A Horan
The Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands
,
S K Durham
The Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands
,
T Kooistra
The Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 15 February 1991

Accepted after revision 20 January 1992

Publication Date:
24 July 2018 (online)

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Summary

Aged rats are more susceptible to endotoxin-induced effects, including microthrombosis and platelet aggregation, than are young rats. To investigate whether changes in the fibrinolytic system might be involved, we investigated the fibrinolytic activity in plasma euglobulin fractions and tissues (lung and heart) of young (6-months old) and aged (24-months old) rats under baseline conditions and after challenge with endotoxin. Aged rats had lower plasma levels of tissue-type plasminogen activator (t-PA) and of urokinase-type PA (u-PA) activity. PA inhibitor (PAI) activity was higher in the plasma of aged rats, as was t-PA activity in lung and heart.

Rats were treated with either a low dose (1 μg/kg) or a high dose (10 mg/kg) of endotoxin. Both treatments induced a transient phase of increased blood fibrinolytic activity, as evidenced by higher levels of tissue-type plasminogen activator (t-PA) activity and decreased levels of PA inhibitor (PAI) activity. Over time, the fibrinolytic activity decreased, probably due to increased levels of PA inhibitor.

Both the early increase in t-PA activity, and the subsequent increase in PAI activity, were more pronounced in the aged rats, as compared with the younger rats, after the high dose of endotoxin. The aged rats also responded to an injection of interleukin-1β or tumor necrosis factor-α with a larger increase of PAI activity than did the younger rats.

Together the data suggest that, compared to young rats, aged rats have a decreased base-line plasma fibrinolytic activity, while their fibrinolytic system is more responsive to challenge by endotoxin and cytokines.

 

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