Direct Vascular Effects of Protease-Activated Receptor Type 1 Agonism In Vivo in Humans
| Autor: | Jillian S Kell, David J. Webb, Ingibjorg Gudmundsdottir, Ian L. Megson, Keith A.A. Fox, David E. Newby, Christopher A. Ludlam |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Agonist medicine.medical_specialty Platelet Aggregation medicine.drug_class Bradykinin Vasodilation Tissue plasminogen activator Cardiovascular Physiological Phenomena chemistry.chemical_compound Von Willebrand factor Physiology (medical) Internal medicine von Willebrand Factor Thrombin receptor medicine Humans Receptor PAR-2 Vasoconstrictor Agents Receptor PAR-1 Platelet Platelet activation biology business.industry Thrombin Platelet Activation Peptide Fragments Endocrinology chemistry Vasoconstriction 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid Tissue Plasminogen Activator Blood Circulation biology.protein Female Vascular Resistance Cardiology and Cardiovascular Medicine business Oligopeptides medicine.drug |
| Zdroj: | Circulation. 114:1625-1632 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circulationaha.106.638478 |
| Popis: | Background— Protease-activated receptor type 1 (PAR-1) has been proposed as the principal thrombin receptor in humans, although its actions in vivo have not been defined. The aim of the present study was to determine the direct vascular actions of PAR-1 agonism in humans. Methods and Results— Dorsal hand vein diameter was measured by the Aellig technique in 14 healthy volunteers during local intravenous SFLLRN (PAR-1 agonist; 0.05 to 15 nmol/min) and SLIGKV (PAR-2 agonist; 1.6 to 160 nmol/min) infusions. The venous effects of SFLLRN were further assessed in the presence or absence of norepinephrine or the glycoprotein IIb/IIIa antagonist tirofiban. Forearm blood flow was measured by venous occlusion plethysmography in 16 volunteers during infusion of SFLLRN (1 to 50 nmol/min), SLIGKV (160 to 800 nmol/min), and the endothelium-dependent vasodilator bradykinin (100 to 1000 pmol/min). Platelet-monocyte binding (a sensitive measure of platelet activation) and plasma tissue plasminogen activator (tPA), plasminogen-activator inhibitor 1, and von Willebrand factor concentrations were measured at intervals throughout the study. SFLLRN caused dose-dependent venoconstriction ( P P P P P P Conclusions— We have demonstrated that PAR-1 agonism causes platelet activation, venous constriction, arterial dilatation, and tPA release in vivo in humans. These unique and contrasting effects provide important insights into the physiological and pathophysiological role of thrombin in the human venous and arterial circulations. |
| Databáze: | OpenAIRE |
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