Effects of BM-573, a thromboxane A2 modulator on systemic hemodynamics perturbations induced by U-46619 in the pig

The aim of our study was to evaluate the effects of thromboxane A2 (TXA2) agonist, U-46619, on systemic circulatory parameters in the pigs before and after administration of a novel TXA2 receptor antagonist and synthase inhibitor (BM-573). Twelve anesthetized pigs were randomly assigned in two group...

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Published in:Prostaglandins & other lipid mediators 2005-12, Vol.78 (1-4), p.82-95
Main Authors: Tchana-Sato, Vincent, Dogné, Jean-Michel, Lambermont, Bernard, Ghuysen, Alexandre, Magis, David, Morimont, Philippe, Hanson, Julien, D'Orio, Vincent, Limet, Raymond, Kolh, Philippe
Format: Article
Language:English
Subjects:
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology
Animals
Hemodynamics - drug effects
In Vitro Techniques
Platelet Aggregation Inhibitors - pharmacology
Sulfonylurea Compounds - pharmacology
Swine
Thromboxane A2 - agonists
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Summary:The aim of our study was to evaluate the effects of thromboxane A2 (TXA2) agonist, U-46619, on systemic circulatory parameters in the pigs before and after administration of a novel TXA2 receptor antagonist and synthase inhibitor (BM-573). Twelve anesthetized pigs were randomly assigned in two groups: in Ago group (n=6), the animals received six consecutive injections of U-46619 at 30 min interval, while in Anta group (n=6) they received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. The effects of each dose of BM-573 on ex vivo platelet aggregation induced by arachidonic acid, collagen or ADP were also evaluated. Vascular properties such as characteristic impedance, peripheral resistance, compliance, arterial elastance were estimated using a windkessel model. Intravenous injections of 0.500 mg/ml of BM-573 and higher doses resulted in a complete inhibition of platelet aggregation induced by arachidonic acid. In the same conditions, BM-573 completely blocked the increase of arterial elastance, and stabilized both mean aortic blood pressure and mean systemic blood flow. In conclusion, BM-573 could therefore be a promising therapeutic approach in pathophysiological states where TXA2 plays a main role in the increase of vascular resistance like in pathologies such as systemic hypertension.
ISSN:1098-8823
DOI:10.1016/j.prostaglandins.2005.04.001