Systemic vascular effects of thrombin and thrombin receptor activating peptide in rats

Thrombosis Research
T SickerE Glusa

Abstract

The proteolytic enzyme thrombin activates its receptor by cleavage of a peptide from the extracellular N-terminus. The newly generated N-terminus acts as a tethered ligand to activate the receptor. Receptor-mediated cellular effects of thrombin can be mimicked by synthetic peptides, which correspond to the amino acid sequence of the newly formed N-terminus. The aim of the present study was to investigate vascular effects of thrombin and the thrombin receptor activating peptide (TRAP: SFLLRN) in vitro and in vivo in rats. In precontracted rat aortic rings, both thrombin (0.3, 1, 3 U/ml) and TRAP (1, 3, 10, 20, 40 microM) induced endothelium-dependent relaxant responses. In anaesthetized rats, the mean arterial blood pressure (MAP) was measured continuously in the carotid artery by a pressure transducer. Thrombin and TRAP were administered as intravenous bolus injection via the femoral vein. Thrombin at doses of 3-100 U/kg, as well as TRAP at doses of 0.1-0.6 mg/kg i.v., caused a reversible decrease in MAP. Administration of TRAP at doses of 0.3 and 0.6 mg/kg led to a triphasic response in most of the animals treated (50% and 75%, respectively), i.e. a short drop of MAP was followed by an increase and finally a longer lasting dec...Continue Reading

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Citations

Sep 12, 2002·Nitric Oxide : Biology and Chemistry·Huige LiUlrich Förstermann
Jan 10, 2013·BMC Medical Genetics·Ndeye Coumba NdiayeSophie Visvikis-Siest
Oct 3, 2006·Journal of Thrombosis and Haemostasis : JTH·F DahmP-A Clavien
Jun 10, 2010·Cardiovascular Therapeutics·Ninian N LangDavid E Newby
Jul 25, 2003·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Hans-Martin Schrödter, Erika Glusa
Sep 29, 2004·Hypertension·Catherine SassSophie Visvikis-Siest
Jan 7, 2006·Journal of Neuroscience Research·Petra Henrich-NoackKlaus G Reymann

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