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 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.
Tchana-Sato
Vincent
V
Hemodynamic Research Center (HemoLiège), University of Liège, Liège 4000, Belgium. tsviny@hotmail.com
Dogné
Jean-Michel
JM
Lambermont
Bernard
B
Ghuysen
Alexandre
A
Magis
David
D
Morimont
Philippe
P
Hanson
Julien
J
D'Orio
Vincent
V
Limet
Raymond
R
Kolh
Philippe
P
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D013552:Swine; D013928:Thromboxane A2 / Q000819:agonists*
C475768:N-terbutyl-N'-(2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl)urea; D010975:Platelet Aggregation Inhibitors; D013453:Sulfonylurea Compounds; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid