Thrombin-induced endothelium-dependent inhibition and direct activation of platelet-vessel wall interaction. Role of prostacyclin, nitric oxide, and thromboxane A2

Détails

ID Serval
serval:BIB_A901B2A954E5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Thrombin-induced endothelium-dependent inhibition and direct activation of platelet-vessel wall interaction. Role of prostacyclin, nitric oxide, and thromboxane A2
Périodique
Circulation
Auteur⸱e⸱s
Yang  Z., Arnet  U., Bauer  E., von Segesser  L., Siebenmann  R., Turina  M., Luscher  T. F.
ISSN
0009-7322
Statut éditorial
Publié
Date de publication
05/1994
Peer-reviewed
Oui
Volume
89
Numéro
5
Pages
2266-72
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Résumé
BACKGROUND: Platelet-vessel wall interaction plays an important role in acute cardiovascular disorders. Thrombin is a potent platelet activator but also has profound effects on the endothelium. Endothelial cells possess antithrombotic activity by releasing nitric oxide and prostacyclin, both potent vasodilators and platelet inhibitors. We studied the role of thrombin as a regulator of platelet-vessel wall interaction in isolated human arteries suspended in organ chambers for isometric tension recording. METHODS AND RESULTS: In arteries with endothelium, thrombin (0.01 to 1 U/mL) induced endothelium-dependent relaxations, which were reduced by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10(-4) mol/L) and/or indomethacin (10(-5) mol/L). Human platelets (75,000/microL) evoked only marginal contractions in arteries with endothelium (3 +/- 3% of the contraction to KCl 100 mmol/L; NS), which were markedly enhanced by endothelial removal (22 +/- 4%; P < .05). Thrombin (1 U/mL) did not affect the response to platelets in arteries with (6 +/- 5%; NS) but induced a huge contraction in rings without endothelium (53 +/- 6%; P < .01 versus control without endothelium). The potent contraction to thrombin-activated platelets (1000 to 75,000/microL) in arteries without endothelium was markedly inhibited by the thromboxane A2 synthetase/receptor antagonist ridogrel (10(-5) mol/L; P < .005 versus control) and the single-acting thromboxane receptor blocker SQ-30741 (10(-7) mol/L; P < .01 versus control). CONCLUSIONS: Thus, thrombin directly stimulates platelets to release thromboxane A2, inducing potent vasoconstriction, which is prevented by the simultaneous thrombin-induced release of prostacyclin and nitric oxide from endothelial cells. In arteries devoid of functional endothelial cells, as occurs in patients with coronary artery disease, a combined inhibition of thromboxane production and action provides a potent therapeutic tool to interfere with the thrombin-induced activation of platelet-vessel wall interaction.
Mots-clé
Coronary Vessels Endothelium, Vascular/drug effects/*physiology Epoprostenol/*physiology Humans Mammary Arteries Nitric Oxide/antagonists & inhibitors/*physiology Platelet Activation/*physiology Platelet Aggregation Inhibitors/*pharmacology Thrombin/*physiology Thromboxane A2/*physiology Vasoconstriction/drug effects/*physiology
Pubmed
Web of science
Création de la notice
14/02/2008 15:16
Dernière modification de la notice
20/08/2019 16:13
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