Cited by 86Coagulation, Bradykinin, Polyphosphates, and AngioedemaBlood Coagulation and Thrombosis MechanismsEicosanoids and Hypertension Pharmacology

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

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Minai, Kazuo, Matsumoto, Tetsuya, Horie, Hajime, Ohira, Naoto, Takashima, Hiroyuki, Yokohama, Hiroshi, Kinoshita, Masahiko·2001·Journal of the American College of Cardiology

Abstract

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 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.

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  • Stimulated t-PA release in the human forearm vasculature correlates with t-PA release in the coronary vasculature.

    “Stimulated t-PA release in the human forearm vasculature correlates with t-PA release in the coronary vasculature”

    From The Vasculature in Prediabetes (2018) · cites this paper as [128]

  • Diminished forearm endothelial t-PA release is associated with an increased risk of cardiovascular events.

    “diminished forearm endothelial t-PA release is associated with an increased risk of cardiovascular events.”

    From The Vasculature in Prediabetes (2018) · cites this paper as [128]

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Research works printed but not linked: 3

  1. Jansson JH, Olofsson BO, Nilsson TK. Predictive value of tissue plasminogen activator mass concentration on long-term mortality in patients with coronary artery disease. Circulation 1993;88:2030 -4.
  2. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 1992;327:669 -77.
  3. Ridker PM, Gaboury CL, Conlin PR, Seely EW, Williams GH, Vaughan DE. Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II. Circulation 1993;87:1969 -73.

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Authors
Minai, K., Matsumoto, T., Horie, H., Ohira, N., Takashima, H., Yokohama, H., & Kinoshita, M.
Affiliations
Shiga University of Medical Science (JP)
Corresponding author
Matsumoto, Tetsuya
Venue
Journal of the American College of Cardiology
Publisher
Elsevier BV
Published
2001-05
Volume
37
Issue
6
Pages
1565-1570
ISSN
0735-1097 (ISSN-L)
OpenAlex
W2021577809
Cited by
86
References
28
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 6 · 2014: 1 · 2013: 3 · 2012: 3
FWCI
5.08
Type
journal article
Language
en
Open access
Locations
  • Journal of the American College of Cardiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords
bradykinin, tissue plasminogen activator, ACE inhibitors, enalapril, coronary circulation, fibrinolysis, plasminogen activator inhibitor-1, coronary blood flow, endothelial cells, atypical chest pain
MeSH terms
Acetylcholine, Analysis of Variance, Angiotensin-Converting Enzyme Inhibitors, Blood Flow Velocity, Bradykinin, Chest Pain, Coronary Circulation, Drug Synergism, Enalapril, Female, Fibrinolysis, Cardiac Catheterization, Hemodynamics, Humans, Male, Middle Aged, Papaverine, Tissue Plasminogen Activator, Vasodilator Agents, Echocardiography, Doppler, Coronary Angiography, Myocardial Ischemia

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