Selective Stimulation of Tissue-Type Plasminogen Activator (t-PA) In Vivo by Infusion of Bradykinin

Summary

Angiotensin converting inhibitors (ACEI) not only decrease angiotensin II (Ang II) but also potentiate the effects of bradykinin. Bradykinin is a potent stimulus to tissue type plasminogen activator (t-PA) secretion in animal models. In this study, we tested the hypothesis that bradykinin increases t-PA levels in humans.

Bradykinin was infused in seventeen hypertensive patients randomized to treatment with the ACEIs captopril and quinapril or with placebo. Bradykinin caused a significant decrease in mean arterial pressure (MAP) (p = 0.014) and increase in pulse (p <0.001). ACEI significantly potentiated the hemodynamic effect of bradykinin (p <0.05). Although baseline t-PA antigen levels were similar in the ACEI-treated (6.85 ± 0.85 ng/ml) and placebo-treated (7.85 ± 0.68 ng/ml) subjects, bradykinin caused a significant (p <0.01) increase in t-PA antigen levels (to 19.3 ± 8.2) only in the ACEI-treated patients. This increase in t-PA was independent of activation of the sympathetic nervous system. Bradykinin had no effect on PAI-1 antigen levels.

These in vivo data suggest that infusion of bradykinin results in an increase in circulating t-PA levels without an effect on PAI-1.

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