Natriuretic peptides regulate the expression of tissue factor and PAI-1 in endothelial cells.
In the present study, we demonstrate that brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) interact with angiotensin II (Ang II) in regulative blood coagulation and fibrinolysis by suppressing the expressions of both tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by Ang II. The expressions of TF and PAI-1 mRNA were analyzed by northern blotting methods, and the activities of TF on the surface of rat aortic endothelial cells (RAECs) and PAI-1 in the culture media were respectively measured by chromogenic assay. Both BNP and CNP suppressed the expressions of TF and PAI-1 mRNA induced by Ang II in a time- and concentration-dependent manner via cGMP cascade, which suppressions were accompanied by respective decrease in activities of TF and PAI-1. However, neither the expression of tissue factor pathway inhibitor (TFPI) nor tissue-type plasminogen activator (TPA) mRNA was affected by the treatment of BNP and CNP.
Yoshizumi
M
M
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan. yoshizum@dc4.so-net.ne.jp
Tsuji
H
H
Nishimura
H
H
Masuda
H
H
Kunieda
Y
Y
Kawano
H
H
Kimura
S
S
Sugano
T
T
Kitamura
H
H
Nakagawa
K
K
Nakagawa
M
M
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000096:biosynthesis; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems; D013873:Thionucleotides / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis
D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D013873:Thionucleotides; C051928:lipoprotein-associated coagulation inhibitor; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; D013925:Thromboplastin; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D006152:Cyclic GMP