Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: effects of angiotensin-converting enzyme inhibitors.
OBJECTIVE
The goal of this study was to determine: 1) whether bradykinin (BK) directly stimulates tissue plasminogen activator (tPA) secretion in human coronary circulation, and 2) whether angiotensin-converting enzyme (ACE) inhibition favorably alters the fibrinolytic balance regulated by BK.


BACKGROUND
Bradykinin is a potent stimulator of tPA secretion in endothelial cells; however, the effect of BK on tPA release in the human coronary circulation has not been studied.


METHODS
Fifty-six patients with atypical chest pain were randomly assigned to two groups: 25 patients were treated with the ACE inhibitor enalapril (ACE inhibitor group), and 31 were not treated with ACE inhibitors (non-ACE inhibitor group). Graded doses of BK (0.2, 0.6, 2.0 microg/min), acetylcholine (ACh) (30 microg/min) and papaverine (PA) (12 mg) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS).


RESULTS
Bradykinin induced similar increases in CBF in both groups. The net tPA release induced by BK was dose-dependently increased in both groups, and the extent of that increase in the ACE inhibitor group was greater than that in the non-ACE inhibitor group. Bradykinin did not alter plasminogen activator inhibitor-1 (PAI-1) levels in the Ao or CS in either group. Neither ACh nor PA altered tPA levels or PAI-1 levels in either group.


CONCLUSIONS
Intracoronary infusion of BK stimulates tPA release without causing any change in PAI-1 levels in the human coronary circulation. In addition, this effect of BK is augmented by an ACE inhibitor.
Minai
K
K
First Department of Internal Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Japan.
Matsumoto
T
T
Horie
H
H
Ohira
N
N
Takashima
H
H
Yokohama
H
H
Kinoshita
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000187:drug effects* / Q000502:physiology*; D006328:Cardiac Catheterization; D002637:Chest Pain / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology*; D004357:Drug Synergism; D015150:Echocardiography, Doppler; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D010208:Papaverine / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000187:drug effects* / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D004656:Enalapril; D010208:Papaverine; D010959:Tissue Plasminogen Activator; D000109:Acetylcholine; D001920:Bradykinin