Selective stimulation of tissue-type plasminogen activator (t-PA) in vivo by infusion of bradykinin.
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 increase 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.
Brown
N J
NJ
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6602, USA. nancy.brown@mcmail.vanderbilt.edu
Nadeau
J H
JH
Vaughan
D E
DE
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D000077583:Quinapril; D016032:Randomized Controlled Trials as Topic; D044005:Tetrahydroisoquinolines; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007546:Isoquinolines; D017395:Plasminogen Activator Inhibitor 1; D044005:Tetrahydroisoquinolines; D002216:Captopril; D010959:Tissue Plasminogen Activator; D000077583:Quinapril; D001920:Bradykinin