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Thromb Haemost 1995; 74(03): 980-986
DOI: 10.1055/s-0038-1649859
Original Article
vessel Wall
Schattauer GmbH Stuttgart

Thrombin Prevents the Expression of Inducible Nitric Oxide Synthase in Vascular Smooth Muscle Cells by a Proteolytically-Activated Thrombin Receptor

Valérie B Schini-Kerth
1   The Zentrum der Physiologie, Klinikum der JWG-Universität, Frankfurt, Germany
,
Beate Fißithaler
1   The Zentrum der Physiologie, Klinikum der JWG-Universität, Frankfurt, Germany
,
Thomas T Andersen
2   The Albany Medical College, Albany, NY, USA
,
John W Fenton II
3   The New York State Department of Health, Albany, USA
,
Paul M Vanhoutte
4   The Institut de Recherches Internationales Servier, Courbevoie, France
,
Rudi Busse
1   The Zentrum der Physiologie, Klinikum der JWG-Universität, Frankfurt, Germany
› Author Affiliations
Further Information

Publication History

Received 12 January 1995

Accepted after resubmission 08 May 1995

Publication Date:
09 July 2018 (online)

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Summary

Proteolytically active forms of thrombin (α- and γ-thrombin) and thrombin receptor peptides inhibited the release of nitrite, a stable endproduct of nitric oxide, evoked by interleukin-1 β(IL-1 β) in cultured vascular smooth muscle cells while proteolytically inactive forms [D-Phe-Pro-Arg chloromethyl ketone-α-thrombin (PPACK-α- thrombin) and diisopropylphosphoryl-α-thrombin (DIP-α-thrombin)] had either no or only minimal inhibitory effects. Under bioassay conditions, perfusates from columns containing IL-1 β-activated vascular smooth muscle cells or cells treated with IL-1βplus PPACK-α-thrombin relaxed detector blood vessels. These relaxations were abolished by the inhibitor of nitric oxide synthesis, NG-nitro-L arginine. No relaxations were obtained with untreated cells or IL-1 β-treated cells in the presence of α-thrombin. The expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells by IL-1 β was impaired by α-thrombin. These results demonstrate that thrombin regulates the expression of the inducible nitric oxide synthase at a transcriptional level via the proteolytic activation of the thrombin receptor in vascular smooth muscle cells

 

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