Bradykinin stimulates the release of tissue plasminogen activator in humancoronary circulation: Effects of angiotensin-converting enzyme inhibitors

OBJECTIVES The goal of this study was to determine: 1) whether bradykinin ( BK) directly stimulates tissue plasminogen activator (tPA) secretion in hum an 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 endothelia l cells; however, the effect of BK on tPA release in the human coronary cir culation 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 (A CE inhibitor group), and 31 were not treated with ACE inhibitors (non-ACE i nhibitor group). Graded doses of BK (0.2, 0.6, 2.0 mug/min), acetylcholine (ACh) (30 mug/min) and papaverine (PA) (12 mg) were administered into the l eft coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flo w velocity measurement. Blood samples were taken from the aorta (Ao) and th e 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, a nd 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 a ctivator inhibitor-1 (PAI-1) levels in the Ao or CS in either group. Neithe r ACh nor PA altered tPA levels or PAI-1 levels in either group. CONCLUSIONS Intracoronary infusion of BK stimulates tPA release without cau sing any change in PAI-1 levels in the human coronary circulation. In addit ion, this effect of BK is augmented by an ACE inhibitor. (J Am Coll Cardiol 2001;37:1565-70) (C) 2001 by the American College of Cardiology.