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


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.


CONCLUSIONS
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.
Kimura
Shinzo
S
Second Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, 602-8566, Kyoto, Japan.
Tsuji
Hajime
H
Nishimura
Hiromi
H
Kato
Hisato
H
Ukimura
Naoki
N
Yano
Shingo
S
Kunieda
Yasufumi
Y
Kawano
Hidehiko
H
Nakagawa
Katsumi
K
Nakagawa
Masao
M
D000818:Animals; D001011:Aorta; D001777:Blood Coagulation / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D008074:Lipoproteins / Q000187:drug effects / Q000235:genetics; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism; D013925:Thromboplastin / Q000187:drug effects / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000187:drug effects / Q000235:genetics
D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C051928:lipoprotein-associated coagulation inhibitor; D009569:Nitric Oxide; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator; D001920:Bradykinin