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CLINICAL STUDY: CORONARY ARTERY DISEASE

Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: effects of angiotensin-converting enzyme inhibitors

^a First Department of Internal Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga, Japan

Manuscript received September 12, 2000; revised manuscript received January 12, 2001, accepted January 29, 2001.

Reprint requests and correspondence: Dr. Tetsuya Matsumoto, First Department of Internal Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga 520-2192, Japan
tetsuyam{at}belle.shiga-med.ac.jp

OBJECTIVES

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 µg/min), acetylcholine (ACh) (30 µg/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.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ACh = acetylcholine   ANOVA = analysis of variance   Ao = aorta   BK = bradykinin   CBF = coronary blood flow   CS = coronary sinus   LAD = left anterior descending   MAP = mean arterial pressure   NO = nitric oxide   PAI-1 = plasminogen activator inhibitor-1   PARC = plasma active renin concentration   tPA = tissue plasminogen activator

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