Summary
Desmopressin acetate administration markedly stimulates release of tissue plasminogen
activator (t-PA) from vascular endothelial cells. The mechanism for this effect is
unknown. Because infusion of epinephrine has been shown to increase t-PA levels, we
examined the role of endogenous catecholamine mediation of t-PA release by desmopressin.
Intravenous desmopressin acetate (0.3 μg/kg) was infused over 30 min in 9 controls
and 11 subjects with diabetes mellitus, a condition associated with abnormalities
of the fibrinolytic system. Plasma was collected in the supine, overnight fasted state
at 15 min intervals (0-60 min) for measurement of t-PA activity, t-PA antigen and
fractionated catecholamines. t-PA activity peaked at 30-45 min and subsequently decreased.
The norepinephrine levels paralleled the t-PA activity. t-PA activity increased 10-fold
from 0.14 ± .12 to 1.49 ± 0.79 IU/ml (Mean ± SD) and plasma norepinephrine increased
2- fold from 426 ± 90 to 780 ± 292 pg/ml. However, epinephrine and dopamine levels
did not change significantly. The response to desmopressin of control and diabetic
subjects was not shown to differ and their data were combined. We conclude that desmopressin
increases plasma norepinephrine in addition to t-PA and that the parallel time course
of change suggests a possible role for norepinephrine in mediating endothelial cell
t-PA release.
Keywords
Desmopressin - Norepinephrine - Tissue plasminogen activator release (t-PA) - Catecholamines
- Endothelial cells
