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

Minai, Kazuo; Matsumoto, Tetsuya; Horie, Hajime; Ohira, Naoto; Takashima, Hiroyuki; Yokohama, Hiroshi; Kinoshita, Masahiko

doi:10.1016/s0735-1097(01)01202-5

Cited by 75 publications

(81 citation statements)

References 27 publications

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“…Intracoronary infusion of BK had no effects on PAI-1 levels at the Ao or CS, which was consistent with our previous findings (15).…”

Section: Plasma Levels Of Tpa Antigen and Pai-1 Antigensupporting

confidence: 93%

“…In our previous report, BK stimulated the release of tPA as well as nitric oxide in the human coronary circulation ( 15 ). However, no data are currently available on the relationship between brachial artery FMD and coronary fibrinolytic activity.…”

Section: Introductionmentioning

confidence: 90%

“…After a diagnostic coronary angiography, a 0.014-inch Doppler-tipped guide wire (Jometrics FloWire, JoMed Inc., Rancho Cordova, USA) was advanced through the Judkins catheter, as previously reported (15,17,18). The wire tip was positioned at the area between the proximal and middle segments of the left anterior descending coronary artery that was free of any major branches within 1.0 cm from the tip.…”

Section: Protocolmentioning

confidence: 99%

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Brachial Artery Flow-Mediated Vasodilation Is Correlated with Coronary Vasomotor and Fibrinolytic Responses Induced by Bradykinin

et al. 2005

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“…Intracoronary infusion of BK had no effects on PAI-1 levels at the Ao or CS, which was consistent with our previous findings (15).…”

Section: Plasma Levels Of Tpa Antigen and Pai-1 Antigensupporting

confidence: 93%

Section: Introductionmentioning

confidence: 90%

Section: Protocolmentioning

confidence: 99%

See 1 more Smart Citation

Brachial Artery Flow-Mediated Vasodilation Is Correlated with Coronary Vasomotor and Fibrinolytic Responses Induced by Bradykinin

et al. 2005

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“…The net release of the protein can then be calculated as the difference in veno-arterial plasma concentration multiplied by the local plasma flow ( Figure 6). This technique has been used by several investigators in order to study if there is an acute release of t-PA in response to local infusion of noradrenaline, methacholine, desmopressin, brady-kinin and substance P, and t-PA-release has been demonstrated in the human forearm and coronary vascular bed [89,[151][152][153][154]. With regard to sympathetic activation, our group has demonstrated an induction of t-PA release across the human forearm in response to mental stress [89] and across the coronary and cerebral vascular bed in response to surgical stress [90,155].…”

Section: Resultsmentioning

confidence: 99%

Inhibition of carboxypeptidase U (TAFIa) activity improves rt-PA induced thrombolysis in a dog model of coronary artery thrombosis

Björkman

Abrahamsson

Nerme

et al. 2005

Thrombosis Research

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The physiologically most important activator of intravascular fibrinolysis is tissue-type plasminogen activator (t-PA) released from endothelial cells. In man, sympathomimetic drugs increase the systemic concentration of t-PA. It is therefore of interest to investigate whether cardiac sympathetic activation can induce a local t-PA release, which could counteract intra-coronary clot formation.Thrombolytic therapy with recombinant t-PA (rt-PA) is effective in acute myocardial infarction, but the treatment is limited by a fairly slow reperfusion rate and frequent early reocclusions. A potential mechanism behind early reocclusions might be that active thrombin is released from the thrombus during thrombolytic therapy. Thrombin has recently been shown to activate procarboxypeptidase U, which in its active form (CPU) down-regulates endogenous fibrinolysis. Therefore, one way of improving thrombolytic efficacy may be to combine rt-PA with a lowmolecular weight direct thrombin inhibitor, which theoretically could have a pro-fibrinolytic effect, either by inhibition of fibrin-bound thrombin and/or by inhibition of CPU activation. An alternative way may be direct inhibition of CPU.In a porcine model, experimental activation of cardiac sympathetic nerves by electrical stimulation at 1 and 8 Hz induced 5-and 20-fold increase in the release of both total and active t-PA together with frequency-dependent increases in heart rate, blood pressure, and coronary blood flow. The t-PA release was independent of the heart rate and coronary flow response, but local infusion of isoprenaline suggested that part of the t-PA response was mediated by stimulation of β-adrenergic receptors. Next, we studied the combined effect of rt-PA and thrombin inhibitors (melagatran, hirudin and heparin) in a canine model of copper coil-induced coronary thrombosis. The profibrinolytic effect of rt-PA, either measured as patency rate or time-to-patency, was significantly enhanced with the low-molecular weight direct thrombin inhibitor melagatran, but to a lesser degree by hirudin and heparin. In the same model it was shown that active CPU is produced locally in the coronary vascular bed during both thrombus formation and clot lysis. Inhibition of thrombin attenuated CPU formation and improved patency. A similar effect was obtained with a direct inhibitor of CPU.In conclusion, the coronary t-PA response to sympathetic stimulation may constitute a thromboprotective defence mechanism to counteract its prothrombotic effects on the systemic level. Furthermore, direct thrombin and/or CPU inhibition may be potential targets for prevention of thrombus formation via facilitation of the endogenous fibrinolytic system.

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“…Indeed, there is substantial evidence that exogenous BK stimulates t-PA release from the human forearm vasculature 11 and that ACE inhibition potentiates this effect in the peripheral 12 and coronary vasculature. 13 Although endogenous BK contributes to the hemodynamic effects of acute ACE inhibition, 14 the analogous physiological role in t-PA release has not been explored. Therefore, we tested the hypothesis that ACE inhibition stimulates endothelial t-PA release through an effect on endogenous BK.…”

mentioning

confidence: 99%

Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin

et al. 2003

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Background-Angiotensin-converting enzyme (ACE) inhibition potentiates the tissue-type plasminogen activator (t-PA) response to exogenous bradykinin. This study tested the hypothesis that ACE inhibition increases endothelial t-PA release through endogenous bradykinin. Methods and Results-We measured the effect of intra-arterial enalaprilat (5 g/min) on forearm blood flow (FBF) and net t-PA release before and during intra-arterial infusion of bradykinin (25 to 400 ng/min) and methacholine (3.2 to 12.8 g/min) in 24 smokers pretreated with bradykinin receptor antagonist HOE 140 (100 g/kg intravenously) or vehicle.There was no specific effect of HOE 140 on FBF or forearm vascular resistance (FVR, 29.9Ϯ3.6 versus 29.7Ϯ3.6 mm Hg · mL Ϫ1 · min Ϫ1 · 100 mL Ϫ1 after vehicle and HOE 140, respectively, Pϭ0.956 between groups). Resting FVR decreased during enalaprilat compared with vehicle or HOE 140, but not compared with baseline, and the effect was similar in the 2 groups (22.0Ϯ2.7 and 24.1Ϯ2.9 mm Hg · mL Ϫ1 · min Ϫ1 · 100 mL

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

Abstract: 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.

Cited by 75 publications

References 27 publications

Brachial Artery Flow-Mediated Vasodilation Is Correlated with Coronary Vasomotor and Fibrinolytic Responses Induced by Bradykinin

Brachial Artery Flow-Mediated Vasodilation Is Correlated with Coronary Vasomotor and Fibrinolytic Responses Induced by Bradykinin

Inhibition of carboxypeptidase U (TAFIa) activity improves rt-PA induced thrombolysis in a dog model of coronary artery thrombosis

Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin

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