Bradykinin enhances in vitro procoagulant and antifibrinolytic properties of rat vascular endothelial cells

• Published in: Thrombosis research Vol. 106; no. 1; pp. 41 - 50
• Main Authors: Kimura, Shinzo, Tsuji, Hajime, Nishimura, Hiromi, Kato, Hisato, Ukimura, Naoki, Yano, Shingo, Kunieda, Yasufumi, Kawano, Hidehiko, Nakagawa, Katsumi, Nakagawa, Masao
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 01-04-2002; Elsevier Science
• Subjects: Animals; Aorta; Biological and medical sciences; Blood Coagulation - drug effects; Blood coagulation. Blood cells; Bradykinin; Bradykinin - pharmacology; Dose-Response Relationship, Drug; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods, hemostasis, fibrinolysis; Kinetics; Lipoproteins - drug effects; Lipoproteins - genetics; Male; Molecular and cellular biology; Nitric oxide (NO); Nitric Oxide - biosynthesis; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen activator inhibitor-1 (PAI-1); Rats; Rats, Sprague-Dawley; Receptor, Bradykinin B2; Receptors, Bradykinin - metabolism; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Thromboplastin - drug effects; Thromboplastin - genetics; Tissue factor (TF); Tissue Plasminogen Activator - drug effects; Tissue Plasminogen Activator - genetics; Tissue-type plasminogen activator (TPA); Vascular endothelial cells; Vascular endothelial cells; NO; TPA; BK; mRNA; TFPI; PGI 2; l-Arg; Bradykinin; FBS; d-NAME; ACEI; PAI-1; cDNA; d-Arg; DME; Plasminogen activator inhibitor-1 (PAI-1); Hoe 140; RAECs; l-NAME; Tissue factor (TF); TF; Tissue-type plasminogen activator (TPA); GAPDH; Nitric oxide (NO); ELISA; Animal model; Endothelial cell; Rat; Coagulation; Tissue factor; t-Plasminogen activator; Plasminogen activator inhibitor 1; Human; Serine endopeptidases; Hematology; Enzyme; Rodentia; Peptidases; Vertebrata; Mammalia; Animal; Nitric oxide; Hydrolases; Tissue factor pathway inhibitor
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(02)00070-1

Introduction: Bradykinin (BK) is a biologically active peptides that exerts a broad spectrum of pathophysiological effects mainly by producing nitric oxide (NO) and prostacyclin from vascular endothelial cells. A direct effect of BK on vascular endothelial cells regarding the expression of the regulatory proteins of coagulation and fibrinolysis has not been fully elucidated.
Materials and methods: The effects of BK on the expression of tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), and tissue-type plasminogen activator (TPA) in cultured rat aortic endothelial cells (RAECs) were respectively evaluated by Northern blot and chromogenic assay or enzyme-linked immunosorbent assay (ELISA).
Results: BK significantly increased the expression of TF and PAI-1 in both mRNA and protein levels, but it did not affect the expression of TFPI. Although BK tended to increase TPA mRNA expression, the observed increase was not statistically significant. Those effects are considered to be mediated by B
2 receptor, because B
2 receptor antagonist (Hoe 140) suppressed those mRNA inductions by BK. Furthermore, since those mRNA inductions by BK were enhanced by nitro-
l-arginine-methyl ester (
l-NAME) and attenuated by
l-arginine (
l-Arg), NO was speculated to negatively contribute to the expressions of TF and PAI-1.
Conclusion: BK was indicated to modify the property of vascular endothelial cells to be procoagulant and antifibrinolytic. Those effects of BK were considered to be the net of its direct effect and the effect negatively mediated by NO.