Adrenomedullin inhibits angiotensin II-induced expression of tissue factorand plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells

Citation
T. Sugano et al., Adrenomedullin inhibits angiotensin II-induced expression of tissue factorand plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells, ART THROM V, 21(6), 2001, pp. 1078-1083
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
1079-5642 → ACNP
Volume
21
Issue
6
Year of publication
2001
Pages
1078 - 1083
Database
ISI
SICI code
1079-5642(200106)21:6<1078:AIAIEO>2.0.ZU;2-B
Abstract
Adrenomedullin (AM) is a potent vasodilating peptide having a variety of ph armacological properties mainly in respect to vascular pathophysiology. We have previously demonstrated that angiotensin II (Ang II) or natriuretic pe ptides have influence on the expression of tissue factor (TF) and plasminog en activator inhibitor-1 (PAI-1) in vascular endothelial cells. The aim of this study was to elucidate the effects of AM on TF and PAI-1 mRNA and prot ein expression in endothelial cells. As a result, AM inhibited Ang II-induc ed TF and PAI-1 mRNA expression in a dose-and time-dependent manner. Becaus e the expression of TF and PAI-1 mRNA induced by Ang II was attenuated by t he increase of intracellular concentrations of cAMP by forskolin and 8-brom o-cAMP and because AM increased the intracellular level of cAMP in rat aort ic endothelial cells, it was indicated that the inhibitory effect of AM on the expressions of TF and PAI-1 was mainly mediated by the cAMP-dependent s ignal transduction. Furthermore, the inhibitory effect of AM on TF and PAI- 1 expression was partly attenuated by an NO synthase inhibitor, NG-nitro-L- arginine methyl ester. Tn conclusion, AM is shown to contribute to the regu lation of blood coagulation and fibrinolysis by vascular endothelial cells mainly via the cAMP pathway.