Effects of BM-573, a thromboxane A(2) modulator on systemic hemodynamics perturbations induced by U-46619 in the pig

The aim of our study was to evaluate the effects of thromboxane A(2) (TXA(2)) agonist, U-46619, on systemic circulatory parameters in the pigs before and after administration of a novel TXA(2) 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 TXA(2) plays it main role in the increase of vascular resistance like in pathologies such as systemic hypertension. (c) 2005 Published by Elsevier Inc.